Presented by Alex Rubinsteyn
Next DSS MIA Event - https://datascience.salon/miami/
A short introduction to cancer immunotherapy followed by several machine learning problems which arise from designing personalized cancer vaccines.
Urinary bladder collects urine from the kidney which is then passed through the urethra. Cancer is abnormal growth of cells leading to tumour in urinary bladder. Bladder Cancer is diagnosed with cystoscopy and biopsy . Treatment of Bladder cancer is done as per stage. It includes Radical Cystectomy, Plevic Lymphadenectomy, Ileal conduit, Neobladder as surgical options.
This document provides information about various tumor markers used in urology, including prostate-specific antigen (PSA) markers for prostate cancer screening and diagnosis, tumor markers for testicular cancer such as alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), and urine-based markers for bladder cancer screening like NMP22 and BTA. It also discusses guidelines for PSA screening and interpretation, as well as clinical applications of different tumor markers for diagnosis, prognosis, monitoring treatment response, and detecting recurrence of urological cancers.
Este documento discute os principais instrumentos de política pública ambiental no Brasil. Resume os tipos de instrumentos de comando e controle, econômicos e voluntários utilizados pelo poder público para promover a proteção ambiental, incluindo padrões, licenciamento, tributação, mercados de emissões e acordos voluntários entre o governo e empresas. Explica brevemente como cada instrumento funciona e quais são os principais debates em torno de sua eficácia.
01 Presentation I VS (8-55MB)- (3-28-08).ppsvshidham
Part I of Four part symposium: “Diagnostic Cytopathology of Serous Effusion” on April 19, 2007 at Neenah, WI, USA
(2008 Wisconsin Society of Cytology, 40th Anniversary)
Peritoneal Carcinomatosis : Dr Amit DangiDr Amit Dangi
Here are the key steps:
1. The left subphrenic space is entered by incising the peritoneum overlying the left hemidiaphragm.
2. The peritoneum is dissected off the left hemidiaphragm in a cephalad direction towards the diaphragmatic crus.
3. The peritoneum is then stripped down the left paracolic gutter towards the pelvis, removing all peritoneal surfaces.
4. The left subphrenic peritonectomy is then completed, exposing the left hemidiaphragm and removing all peritoneal surfaces in the left subphrenic space.
Slide livro Sociologia ensino médio capitulo 22 do Tomazipascoalnaib
O documento discute diferentes tipos de revolução e transformação social ao longo da história. Aborda revoluções como a Industrial, Agrícola e Francesa, além de revoluções comunistas na Rússia e China no século XX. Também menciona revoluções no México e em Cuba. Em geral, as revoluções objetivavam mudar estruturas sociais, políticas e econômicas, embora nem sempre tenham alcançado liberdade e emancipação.
Renal transplantation involves selecting recipients by diagnosing their primary kidney disease, ruling out active infections or malignancies, and assessing operative risks. Suitable living donors undergo evaluation with CT angiography and surgery to remove a kidney, with efforts to minimize warm ischemia time and preserve vessel length. The donated kidney is preserved through simple cold storage before transplantation via vascular anastomosis and ureter reimplantation during the recipient's operation. Lifelong immunosuppression is required post-operatively to prevent rejection, while infection risk remains.
Non-muscle-invasive bladder cancer is typically treated with transurethral resection of bladder tumors (TURBT) to diagnose, stage, and remove visible tumors, followed by intravesical chemotherapy or immunotherapy to prevent recurrence depending on risk level. Bacillus Calmette-Guerin (BCG) immunotherapy is recommended for high-risk non-muscle-invasive bladder cancer to elicit an immune response against tumor cells. Patients undergo cystoscopy surveillance following treatment to monitor for recurrence.
Urinary bladder collects urine from the kidney which is then passed through the urethra. Cancer is abnormal growth of cells leading to tumour in urinary bladder. Bladder Cancer is diagnosed with cystoscopy and biopsy . Treatment of Bladder cancer is done as per stage. It includes Radical Cystectomy, Plevic Lymphadenectomy, Ileal conduit, Neobladder as surgical options.
This document provides information about various tumor markers used in urology, including prostate-specific antigen (PSA) markers for prostate cancer screening and diagnosis, tumor markers for testicular cancer such as alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), and urine-based markers for bladder cancer screening like NMP22 and BTA. It also discusses guidelines for PSA screening and interpretation, as well as clinical applications of different tumor markers for diagnosis, prognosis, monitoring treatment response, and detecting recurrence of urological cancers.
Este documento discute os principais instrumentos de política pública ambiental no Brasil. Resume os tipos de instrumentos de comando e controle, econômicos e voluntários utilizados pelo poder público para promover a proteção ambiental, incluindo padrões, licenciamento, tributação, mercados de emissões e acordos voluntários entre o governo e empresas. Explica brevemente como cada instrumento funciona e quais são os principais debates em torno de sua eficácia.
01 Presentation I VS (8-55MB)- (3-28-08).ppsvshidham
Part I of Four part symposium: “Diagnostic Cytopathology of Serous Effusion” on April 19, 2007 at Neenah, WI, USA
(2008 Wisconsin Society of Cytology, 40th Anniversary)
Peritoneal Carcinomatosis : Dr Amit DangiDr Amit Dangi
Here are the key steps:
1. The left subphrenic space is entered by incising the peritoneum overlying the left hemidiaphragm.
2. The peritoneum is dissected off the left hemidiaphragm in a cephalad direction towards the diaphragmatic crus.
3. The peritoneum is then stripped down the left paracolic gutter towards the pelvis, removing all peritoneal surfaces.
4. The left subphrenic peritonectomy is then completed, exposing the left hemidiaphragm and removing all peritoneal surfaces in the left subphrenic space.
Slide livro Sociologia ensino médio capitulo 22 do Tomazipascoalnaib
O documento discute diferentes tipos de revolução e transformação social ao longo da história. Aborda revoluções como a Industrial, Agrícola e Francesa, além de revoluções comunistas na Rússia e China no século XX. Também menciona revoluções no México e em Cuba. Em geral, as revoluções objetivavam mudar estruturas sociais, políticas e econômicas, embora nem sempre tenham alcançado liberdade e emancipação.
Renal transplantation involves selecting recipients by diagnosing their primary kidney disease, ruling out active infections or malignancies, and assessing operative risks. Suitable living donors undergo evaluation with CT angiography and surgery to remove a kidney, with efforts to minimize warm ischemia time and preserve vessel length. The donated kidney is preserved through simple cold storage before transplantation via vascular anastomosis and ureter reimplantation during the recipient's operation. Lifelong immunosuppression is required post-operatively to prevent rejection, while infection risk remains.
Non-muscle-invasive bladder cancer is typically treated with transurethral resection of bladder tumors (TURBT) to diagnose, stage, and remove visible tumors, followed by intravesical chemotherapy or immunotherapy to prevent recurrence depending on risk level. Bacillus Calmette-Guerin (BCG) immunotherapy is recommended for high-risk non-muscle-invasive bladder cancer to elicit an immune response against tumor cells. Patients undergo cystoscopy surveillance following treatment to monitor for recurrence.
Benign Biliary Stricture is a common condition which we encounter during gastro practice. Here we discuss in detail about its diagnosis and management.
A democracia está em crise? O documento discute conceitos de democracia e liberdade e analisa a situação da democracia no Brasil, apontando desafios como a crise da representatividade política revelada pelos protestos de 2013 e a necessidade de mais diálogo entre representantes e sociedade.
ANDROGEN DEPRIVATION THERAPHY ON PRASTATE CAEko indra
Androgen deprivation therapy (ADT) reduces androgen hormone levels to prevent prostate cancer growth. It can be administered medically or surgically. Medically, it involves using LH-RH agonists or antagonists to inhibit testosterone production, or anti-androgens to block the androgen receptor. Surgically, bilateral orchiectomy quickly reduces testosterone levels. ADT is indicated for high risk and metastatic prostate cancer, and is often used with radiation therapy. The goal is to lower testosterone levels below 50 ng/dL to achieve a castration effect.
Este documento descreve a ruptura entre o estilo Barroco e o Maneirismo na arte. O Maneirismo antecedeu o Barroco e apresentou características mais livres e extravagantes em comparação ao rigor renascentista. Já o Barroco focou mais na emotividade e ilusão, usando efeitos como curvas e luz para criar a impressão de movimento. O documento também discute as diferenças nas características arquitetônicas, esculturais e pictóricas entre os dois estilos.
Prevention and management of complications of pancreatic surgeryzeeshanrahman86
This document summarizes key complications of pancreatic surgery and strategies for prevention and management. The three most common complications are delayed gastric emptying (14%), wound infection (7%), and pancreatic fistula (5%). Mortality has decreased in high-volume centers to 5% while morbidity remains around 35-50%. Prevention focuses on risk stratification and measures like duct-to-mucosa suturing. Management involves NPO, TPN, antibiotics, imaging-guided drainage and re-exploration if needed.
Therapeutic Cancer Vaccines: Where Predictive Models MatterTimothy O'Donnell
Cancer vaccines targeting mutated tumor proteins are an emerging personalized medicine. In a number of clinical trials evaluating these therapies, including several at our institution, each patient's vaccine is individually formulated based on the unique mutations present in his or her tumor. As experimentally testing vaccine immunogenicity is infeasible in this setting, these therapies rely on computational prediction of vaccine immunogenicity. In this talk I will discuss recent work to accurately predict T cell epitopes, focusing on development of the MHCflurry software package for CD8+ T cell epitope prediction (https://github.com/openvax/mhcflurry). I will also touch on other, less studied modeling tasks that may help improve cancer vaccines in the future.
Crosstalk Between Cancer Inflammation and Immunity: Host Defense Webinar Seri...QIAGEN
This slidedeck will review the mechanisms of anticancer immune responses, which include immune checkpoints and the cross-talk between cancer cells and the cellular mediators of inflammation and immunity. The impact of gut microbiota in eliciting the immune responses against cancer and modulating the effects of drugs will also be discussed. In addition, we will discuss the roles of long non-coding RNAs (lncRNAs) in cancer progression and immune responses. Research tools and therapeutic strategies are also presented.
This document provides an overview of principles of cancer immunotherapy. It discusses anti-cancer immunity mechanisms like antigen presentation and T cell activation. It also examines how cancers can evade the immune system through strategies like low MHC expression and immunosuppressive factors. The document then reviews clinical applications of immunotherapy including cytokines, monoclonal antibodies, adoptive cell transfer, vaccines, and checkpoint inhibitors. Combination therapies are showing promise for enhancing anti-tumor responses.
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
Immuno-oncology Discoveries, University of Chicagouchicagotech
The University of Chicago has a leading Immuno-Oncology program that takes a multi-faceted approach to cancer immunotherapy through innovative translational research. The program focuses on immune stimulation, checkpoint blockade, vaccines, and diagnostics to develop new immunotherapies. Representative technologies highlighted include using LIGHT to stimulate anti-tumor immune responses, reversing T-cell anergy with DGK inhibitors, developing senescent cell and antibody-based vaccines, and biomarkers to identify responsive patients. The university has extensive clinical trial capabilities and core facilities to support research and translation.
This document summarizes the history and development of cancer vaccines from early experiments in mice to current human clinical trials. It discusses key concepts like antigen presentation and types of vaccine components. Murine studies showed synergistic effects of combining vaccines with checkpoint inhibitors. Human trials demonstrated the first FDA-approved therapeutic cancer vaccine Provenge for prostate cancer in 2010 and the oncolytic virus therapy T-VEC for melanoma in 2015. Data from the NCI Surgery Branch showed durable responses in some patients treated with personalized peptide vaccines.
This document discusses tumor immunity and the immune system's response to tumors. It begins with an introduction and outlines the aim and objectives. It then covers basic concepts of tumor immunity including tumor antigens and anti-tumor effector mechanisms. It discusses immunosurveillance and immunoediting of cancer and how tumors can evade the immune system. It also touches on laboratory investigation, cancer vaccine development, cancer immunotherapy, and conclusions. The overall goal is to explain how the immune system responds to tumors and the complex relationship between immunity and tumor development.
Advaxis is developing a personalized neoepitope immunotherapy called ADXS-NEO to target mutations specific to a patient's cancer. Recent advances in genomics, immunotherapy, and cancer biology have enabled a new understanding of cancer as unique to each patient. ADXS-NEO uses DNA sequencing to identify tumor-specific mutations, engineers these neoepitopes into a bacterial vector, and administers this to activate the patient's immune system to target and eliminate the cancer. Advaxis has several clinical programs testing this approach across multiple cancer types with the goal of empowering each patient's immune system to fight their own unique form of cancer.
Question of Quality Conference 2016 - Personalized Cancer MedicineHCA Healthcare UK
This document summarizes a presentation on personalized cancer medicine. It discusses:
1. A brief history of precision oncology, from identifying the Philadelphia chromosome in 1960 to recent advances in immunotherapy.
2. The concept of driver mutations that directly or indirectly confer growth advantages to cancer cells and have clinical implications for diagnosis, prognosis, or targeted therapies.
3. How next-generation sequencing can best identify all four classes of genomic alterations that drive tumor growth by sequencing both DNA and RNA.
4. Some case histories where genomic profiling identified targetable alterations and patients benefited from matched targeted therapies.
5. Concluding thoughts on the complexity of the cancer genome and how comprehensive genomic profiling is enabling evidence-based
Tariq Mughal discusses personalized cancer medicine and highlights some key points:
1. Precision medicine has evolved greatly over the past few decades from basic cytogenetics and hormone therapies to comprehensive genomic profiling and immunotherapy. Targeted therapies are revolutionizing cancer treatment.
2. Driver mutations directly or indirectly confer a growth advantage to cancer cells and have clinical implications for diagnosis, prognosis, and targeted therapies. Comprehensive genomic profiling using next-generation sequencing can best identify all classes of driver mutations.
3. Case histories demonstrate how genomic profiling can identify targetable genomic alterations like ERBB2 mutations, ALK fusions, and FBXW7 mutations and guide treatment with targeted therapies, often with dramatic responses
This document summarizes Targovax's approach to activating the immune system to fight cancer. It discusses moving from sequential treatment strategies like surgery, radiation, and chemotherapy to a combination approach harnessing the immune system. Targovax's focus is on immune activators like oncolytic viruses and vaccines to make cancer visible to the immune system. The document outlines Targovax's clinical programs using oncolytic viruses ONCOS and therapeutic cancer vaccine TG, including current and planned trials in cancers like mesothelioma, melanoma, and colorectal cancer. Early data from a phase I/II trial of ONCOS-102 in mesothelioma shows safety and signs of efficacy.
Immunotherapy is a treatment method for brain tumors that works by activating or suppressing the immune system. There are several types of immunotherapy including monoclonal antibody therapy, CAR T-cell therapy, checkpoint inhibitors, dendritic cell vaccines, and oncolytic viruses. Monoclonal antibodies target specific proteins on cancer cells to help the immune system find and kill them, while CAR T-cell therapy uses modified T cells to recognize and bind to tumor cells. Checkpoint inhibitors block proteins that stop the immune system from attacking cancer cells. Despite ongoing research, many immunotherapy techniques still face challenges in overcoming the blood-brain barrier and immunosuppressive environment of brain tumors.
This document discusses various types of cancer immunotherapy, including dendritic cell vaccines, antibody therapy, and cytokine therapy. Dendritic cell vaccines work by activating dendritic cells with tumor antigens, which then provoke an immune response against cancer cells. Antibody therapy targets specific cancer antigens and uses mechanisms like complement-dependent cytotoxicity to kill cancer cells. Cytokines like interferons are also used to treat cancer by activating immune cells and inducing anti-tumor responses. Immunotherapy holds promise for harnessing the power of the immune system to fight cancer.
Robert Anders, MD, PhD, Julie R. Brahmer, MD, MSc, and Christopher D. Gocke, MD, prepared useful Practice Aids pertaining to immunotherapy and biomarker testing for this CME/MOC/CC activity titled "Keeping Up With Advances in Cancer Immunotherapy and Biomarker Testing: Implications for Pathologists at the Forefront of the Emerging Precision Immuno-Oncology Era." For the full presentation, monograph, complete CME/MOC/CC information, and to apply for credit, please visit us at http://bit.ly/2L7zlSy. CME/MOC/CC credit will be available until May 2, 2020.
This document discusses personalized cancer vaccines created using neoantigens unique to a patient's tumor. The process involves procuring tumor cells from the patient for genetic sequencing to identify neoantigens. Predicted mutated peptides likely to bind the patient's HLA proteins are then synthesized into a personalized vaccine administered to the patient to trigger an immune response against tumors containing the same neoantigens. The company discussed offers DNA/RNA sequencing, neoantigen prediction and personalized vaccine manufacturing services.
Cancer immunotherapy utilizes the immune system to recognize and destroy cancer cells. There are several types of immunotherapy including cancer vaccines, adoptive cell transfer, checkpoint inhibitors, and oncolytic viruses. Cancer vaccines educate the immune system to recognize tumor antigens while adoptive cell transfer involves extracting immune cells from patients and expanding tumor-specific T cells ex vivo for reinfusion. Checkpoint inhibitors like anti-CTLA4 and anti-PD1 antibodies block inhibitory pathways and unleash existing anti-tumor immune responses. Oncolytic viruses selectively infect and lyse tumor cells and stimulate antitumor immunity through antigen release.
Benign Biliary Stricture is a common condition which we encounter during gastro practice. Here we discuss in detail about its diagnosis and management.
A democracia está em crise? O documento discute conceitos de democracia e liberdade e analisa a situação da democracia no Brasil, apontando desafios como a crise da representatividade política revelada pelos protestos de 2013 e a necessidade de mais diálogo entre representantes e sociedade.
ANDROGEN DEPRIVATION THERAPHY ON PRASTATE CAEko indra
Androgen deprivation therapy (ADT) reduces androgen hormone levels to prevent prostate cancer growth. It can be administered medically or surgically. Medically, it involves using LH-RH agonists or antagonists to inhibit testosterone production, or anti-androgens to block the androgen receptor. Surgically, bilateral orchiectomy quickly reduces testosterone levels. ADT is indicated for high risk and metastatic prostate cancer, and is often used with radiation therapy. The goal is to lower testosterone levels below 50 ng/dL to achieve a castration effect.
Este documento descreve a ruptura entre o estilo Barroco e o Maneirismo na arte. O Maneirismo antecedeu o Barroco e apresentou características mais livres e extravagantes em comparação ao rigor renascentista. Já o Barroco focou mais na emotividade e ilusão, usando efeitos como curvas e luz para criar a impressão de movimento. O documento também discute as diferenças nas características arquitetônicas, esculturais e pictóricas entre os dois estilos.
Prevention and management of complications of pancreatic surgeryzeeshanrahman86
This document summarizes key complications of pancreatic surgery and strategies for prevention and management. The three most common complications are delayed gastric emptying (14%), wound infection (7%), and pancreatic fistula (5%). Mortality has decreased in high-volume centers to 5% while morbidity remains around 35-50%. Prevention focuses on risk stratification and measures like duct-to-mucosa suturing. Management involves NPO, TPN, antibiotics, imaging-guided drainage and re-exploration if needed.
Therapeutic Cancer Vaccines: Where Predictive Models MatterTimothy O'Donnell
Cancer vaccines targeting mutated tumor proteins are an emerging personalized medicine. In a number of clinical trials evaluating these therapies, including several at our institution, each patient's vaccine is individually formulated based on the unique mutations present in his or her tumor. As experimentally testing vaccine immunogenicity is infeasible in this setting, these therapies rely on computational prediction of vaccine immunogenicity. In this talk I will discuss recent work to accurately predict T cell epitopes, focusing on development of the MHCflurry software package for CD8+ T cell epitope prediction (https://github.com/openvax/mhcflurry). I will also touch on other, less studied modeling tasks that may help improve cancer vaccines in the future.
Crosstalk Between Cancer Inflammation and Immunity: Host Defense Webinar Seri...QIAGEN
This slidedeck will review the mechanisms of anticancer immune responses, which include immune checkpoints and the cross-talk between cancer cells and the cellular mediators of inflammation and immunity. The impact of gut microbiota in eliciting the immune responses against cancer and modulating the effects of drugs will also be discussed. In addition, we will discuss the roles of long non-coding RNAs (lncRNAs) in cancer progression and immune responses. Research tools and therapeutic strategies are also presented.
This document provides an overview of principles of cancer immunotherapy. It discusses anti-cancer immunity mechanisms like antigen presentation and T cell activation. It also examines how cancers can evade the immune system through strategies like low MHC expression and immunosuppressive factors. The document then reviews clinical applications of immunotherapy including cytokines, monoclonal antibodies, adoptive cell transfer, vaccines, and checkpoint inhibitors. Combination therapies are showing promise for enhancing anti-tumor responses.
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
Immuno-oncology Discoveries, University of Chicagouchicagotech
The University of Chicago has a leading Immuno-Oncology program that takes a multi-faceted approach to cancer immunotherapy through innovative translational research. The program focuses on immune stimulation, checkpoint blockade, vaccines, and diagnostics to develop new immunotherapies. Representative technologies highlighted include using LIGHT to stimulate anti-tumor immune responses, reversing T-cell anergy with DGK inhibitors, developing senescent cell and antibody-based vaccines, and biomarkers to identify responsive patients. The university has extensive clinical trial capabilities and core facilities to support research and translation.
This document summarizes the history and development of cancer vaccines from early experiments in mice to current human clinical trials. It discusses key concepts like antigen presentation and types of vaccine components. Murine studies showed synergistic effects of combining vaccines with checkpoint inhibitors. Human trials demonstrated the first FDA-approved therapeutic cancer vaccine Provenge for prostate cancer in 2010 and the oncolytic virus therapy T-VEC for melanoma in 2015. Data from the NCI Surgery Branch showed durable responses in some patients treated with personalized peptide vaccines.
This document discusses tumor immunity and the immune system's response to tumors. It begins with an introduction and outlines the aim and objectives. It then covers basic concepts of tumor immunity including tumor antigens and anti-tumor effector mechanisms. It discusses immunosurveillance and immunoediting of cancer and how tumors can evade the immune system. It also touches on laboratory investigation, cancer vaccine development, cancer immunotherapy, and conclusions. The overall goal is to explain how the immune system responds to tumors and the complex relationship between immunity and tumor development.
Advaxis is developing a personalized neoepitope immunotherapy called ADXS-NEO to target mutations specific to a patient's cancer. Recent advances in genomics, immunotherapy, and cancer biology have enabled a new understanding of cancer as unique to each patient. ADXS-NEO uses DNA sequencing to identify tumor-specific mutations, engineers these neoepitopes into a bacterial vector, and administers this to activate the patient's immune system to target and eliminate the cancer. Advaxis has several clinical programs testing this approach across multiple cancer types with the goal of empowering each patient's immune system to fight their own unique form of cancer.
Question of Quality Conference 2016 - Personalized Cancer MedicineHCA Healthcare UK
This document summarizes a presentation on personalized cancer medicine. It discusses:
1. A brief history of precision oncology, from identifying the Philadelphia chromosome in 1960 to recent advances in immunotherapy.
2. The concept of driver mutations that directly or indirectly confer growth advantages to cancer cells and have clinical implications for diagnosis, prognosis, or targeted therapies.
3. How next-generation sequencing can best identify all four classes of genomic alterations that drive tumor growth by sequencing both DNA and RNA.
4. Some case histories where genomic profiling identified targetable alterations and patients benefited from matched targeted therapies.
5. Concluding thoughts on the complexity of the cancer genome and how comprehensive genomic profiling is enabling evidence-based
Tariq Mughal discusses personalized cancer medicine and highlights some key points:
1. Precision medicine has evolved greatly over the past few decades from basic cytogenetics and hormone therapies to comprehensive genomic profiling and immunotherapy. Targeted therapies are revolutionizing cancer treatment.
2. Driver mutations directly or indirectly confer a growth advantage to cancer cells and have clinical implications for diagnosis, prognosis, and targeted therapies. Comprehensive genomic profiling using next-generation sequencing can best identify all classes of driver mutations.
3. Case histories demonstrate how genomic profiling can identify targetable genomic alterations like ERBB2 mutations, ALK fusions, and FBXW7 mutations and guide treatment with targeted therapies, often with dramatic responses
This document summarizes Targovax's approach to activating the immune system to fight cancer. It discusses moving from sequential treatment strategies like surgery, radiation, and chemotherapy to a combination approach harnessing the immune system. Targovax's focus is on immune activators like oncolytic viruses and vaccines to make cancer visible to the immune system. The document outlines Targovax's clinical programs using oncolytic viruses ONCOS and therapeutic cancer vaccine TG, including current and planned trials in cancers like mesothelioma, melanoma, and colorectal cancer. Early data from a phase I/II trial of ONCOS-102 in mesothelioma shows safety and signs of efficacy.
Immunotherapy is a treatment method for brain tumors that works by activating or suppressing the immune system. There are several types of immunotherapy including monoclonal antibody therapy, CAR T-cell therapy, checkpoint inhibitors, dendritic cell vaccines, and oncolytic viruses. Monoclonal antibodies target specific proteins on cancer cells to help the immune system find and kill them, while CAR T-cell therapy uses modified T cells to recognize and bind to tumor cells. Checkpoint inhibitors block proteins that stop the immune system from attacking cancer cells. Despite ongoing research, many immunotherapy techniques still face challenges in overcoming the blood-brain barrier and immunosuppressive environment of brain tumors.
This document discusses various types of cancer immunotherapy, including dendritic cell vaccines, antibody therapy, and cytokine therapy. Dendritic cell vaccines work by activating dendritic cells with tumor antigens, which then provoke an immune response against cancer cells. Antibody therapy targets specific cancer antigens and uses mechanisms like complement-dependent cytotoxicity to kill cancer cells. Cytokines like interferons are also used to treat cancer by activating immune cells and inducing anti-tumor responses. Immunotherapy holds promise for harnessing the power of the immune system to fight cancer.
Robert Anders, MD, PhD, Julie R. Brahmer, MD, MSc, and Christopher D. Gocke, MD, prepared useful Practice Aids pertaining to immunotherapy and biomarker testing for this CME/MOC/CC activity titled "Keeping Up With Advances in Cancer Immunotherapy and Biomarker Testing: Implications for Pathologists at the Forefront of the Emerging Precision Immuno-Oncology Era." For the full presentation, monograph, complete CME/MOC/CC information, and to apply for credit, please visit us at http://bit.ly/2L7zlSy. CME/MOC/CC credit will be available until May 2, 2020.
This document discusses personalized cancer vaccines created using neoantigens unique to a patient's tumor. The process involves procuring tumor cells from the patient for genetic sequencing to identify neoantigens. Predicted mutated peptides likely to bind the patient's HLA proteins are then synthesized into a personalized vaccine administered to the patient to trigger an immune response against tumors containing the same neoantigens. The company discussed offers DNA/RNA sequencing, neoantigen prediction and personalized vaccine manufacturing services.
Cancer immunotherapy utilizes the immune system to recognize and destroy cancer cells. There are several types of immunotherapy including cancer vaccines, adoptive cell transfer, checkpoint inhibitors, and oncolytic viruses. Cancer vaccines educate the immune system to recognize tumor antigens while adoptive cell transfer involves extracting immune cells from patients and expanding tumor-specific T cells ex vivo for reinfusion. Checkpoint inhibitors like anti-CTLA4 and anti-PD1 antibodies block inhibitory pathways and unleash existing anti-tumor immune responses. Oncolytic viruses selectively infect and lyse tumor cells and stimulate antitumor immunity through antigen release.
This document discusses Targovax's focus on immune activators to treat cancer. It summarizes:
1) Targovax's approach of using oncolytic viruses and vaccines to activate T-cells to target tumors, rather than directly targeting cancer through surgery, radiation, or chemotherapy.
2) Targovax's two programs - ONCOS, an oncolytic virus, and TG, a therapeutic cancer vaccine - and their clinical development strategies.
3) Early positive results from a Phase I/II trial of ONCOS-102 for malignant pleural mesothelioma, with the drug showing safety, innate and adaptive immune activation, and early signs of clinical activity.
This article discusses recent advances in understanding the immune system's response to cancer. It identifies three key points:
1) Tumor antigens that the immune system can recognize have been identified, including molecules that are unique to cancer cells (tumor-specific) and molecules expressed differently by cancer and normal cells (tumor-associated). Over 100 peptides have been identified, some from unique mutations and most from proteins differentially expressed in tumors.
2) Cancers can elicit inflammatory responses through danger signals and tumor antigens, supporting the concept of "immunosurveillance" where the immune system recognizes and eliminates malignant cells. However, tumors can also suppress immunity through mechanisms like regulatory T cells and immunosuppressive enzymes.
This document summarizes cellular therapy approaches for multiple myeloma, including:
1) Allogeneic stem cell transplantation can exploit the graft-versus-myeloma effect but is associated with transplant-related mortality; reduced intensity conditioning regimens may improve outcomes.
2) Vaccine strategies targeting antigens like MAGE and idiotype have shown safety and immune responses in clinical trials but limited clinical responses so far.
3) Adoptive transfer of chimeric antigen receptor (CAR) T cells and natural killer (NK) cells show pre-clinical activity against myeloma and are being tested in early clinical trials.
4) Ex-vivo expanded cord blood NK cells are being tested in a clinical
This document discusses cancer vaccines as a novel approach to treating and preventing cancer. It defines cancer vaccines and explains the different types, including dendritic cell vaccines, antigen vaccines, tumor cell vaccines, DNA vaccines, and anti-idiotype vaccines. Several examples of cancer vaccines currently in clinical trials are provided, such as OncoVAX for colon cancer and Provenge for prostate cancer. While progress has been made, more research is still needed before cancer vaccines can be widely used in clinical settings.
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Next DSS MIA Event - https://datascience.salon/miami/
Next DSS AUS Event - https://datascience.salon/austin/
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After each of the above steps, we will explore how the information extracted can be used for customer segmentation based on a similarity measure. Specifically, we will focusing on how each stage affects the similarity between pages. Through this exploration, participants will gain an understanding of how different processing may be appropriate for different NLP use-cases. For example, fitting topic models to document vectors is most useful when there is likely to be a distinct set of topics among the document set.
The workshop will conclude with a discussion about how these techniques are currently used in production at ThriveHive. This will provide participants with an example of how they might be able to make use of what we explored in their own work. Any additional time will be devoted to discussing advanced techniques in NLP such as text autoencoders for computing context-sensitive similarity between documents.
Data Science Salon: nterpretable Predictive Models in the Healthcare DomainFormulatedby
Predictive models are often used to identify individuals that will likely have escalating health severity in the future and accordingly deliver appropriate interventions. However, for the clinicians and care managers, these predictive models often act as a black-box at an individual level. The reason for this being, typically predictive models use combinations of complicated algorithms that makes it hard to explain the reason behind a predictive model score at an individual level. This talk will focus on model and feature agnostic methodologies and techniques that help uncover the drivers behind a prediction at a personal level in a healthcare setting.
Next DSS MIA Event - https://datascience.salon/miami/
Next DSS AUS Event - https://datascience.salon/austin/
Data Science Salon: Applications of Embeddings and Deep Learning at GrouponFormulatedby
Bojan Babick, Senior Software Engineer at Groupon talks about how the Groupon technical team went on a journey to switch from rule-based systems to classical machine learning models with hand-designed features to representation learning and deep learning
See the related post here: https://roundtable.datascience.salon/applications-of-embeddings-and-deep-learning-at-groupon
Sign up for DSSInsider to see the full video: https://insider.datascience.salon/
Next DSS SEA Event - https://datascience.salon/seattle/
Data Science Salon: Kaggle 1st Place in 30 minutes: Putting AutoML to Work wi...Formulatedby
Presented by Hila Lamm, Chief Strategy Officer at Firefly.ai
Next DSS MIA Event - https://datascience.salon/miami/
Next DSS AUS Event - https://datascience.salon/austin/
With all the hype around auto machine learning for computer vision, businesses with structured data are left wondering: Is AutoML relevant for enterprise data? Can it alleviate the bottleneck that data science teams are experiencing?
Our team was experimenting with different types of enterprise challenges -- from optimizing pricing to credit card fraud detection to retail banking customer behavior -- and was able to automatically build models that produced top-ranking Kaggle results within a few hours. In this session, through customer use cases and under the hood insights, you will learn about the capabilities of AutoML as applied on Firefly. Oh, and we’ll also talk about how we attained a Kaggle 1st place score in just half an hour.
Presented by SK Reddy, Chief Product Officer AI at Hexagon
Next DSS MIA Event - https://datascience.salon/miami/
Next DSS AUS Event - https://datascience.salon/austin/
Detecting indoor human activity is used for security, patient care, baby monitoring, etc. purposes. Other than having another human being providing the service (i.e. a security guard, a nurse, baby’s mother, etc.), many solutions have been suggested using image processing neural networks that detect patient’s fall, baby walking, door open, etc. Many of these models have achieved higher prediction accuracy rates. But neural networks that use video cameras bring up privacy concerns.
Custom made sensors, though solve the problem, are expensive. Researchers have proposed deep learning (DL) models use wifi signals to detect human activity. This is relatively recent research.
I would like to discuss on how to design a DL to detect human activity to use Wifi signals that are available from off-the-shelf wifi routers. I will also discuss the architecture of such models, share the implementation problems and evaluate solutions that may address these problems.
Data Science Salon: Building a Data Driven Product MindsetFormulatedby
Presented by Viswanath Puttagunta, Chief Technology Officer of Divergence.AI
Next DSS MIA Event - https://datascience.salon/miami/
Next DSS AUS Event - https://datascience.salon/austin/
OK, your Analysts and ETL developers pushed the limits of Tableau and traditional data warehouses. May be recently, you've even leveraged some of the Cloud services. You have a good idea of key metrics that are critical to your organization. But you definitely know there's a lot more data lurking within your organization that could be monetized. You look around and are overwhelmed with choices. You want a standard set of tools, but the tools are evolving at a dizzying pace, giving you a classic case of analysis paralysis. Even when you pick a tool, getting licenses and on-boarding seems to be taking forever!
Come and learn how to build a ""Data Driven Product Mindset"" within your organization. We will discuss how to build a cross-functional team that has the right basics in AI/ML/Software/DevOps/Admin and can evolve as fast as the evolving tool-set, while providing actionable insights every step of the way. We will delve into the benefits of using Managed & Serverless services in Cloud to make your team nimbler than ever. That team you build will be the most formidable tool your organization will have.
Data Science Salon: Introduction to Machine Learning - Marketing Use CaseFormulatedby
This document provides an introduction and agenda for a machine learning marketing use case presentation. It includes an overview of the data science process, machine learning algorithms, and examples of machine learning in marketing. It discusses data preparation, feature selection, preprocessing, transformation, and algorithm selection. It also provides a primer on deep learning, the benefits of deep learning for feature extraction, and examples of innovations using deep learning. The presentation aims to help understand how to apply machine learning and deep learning techniques to optimize marketing.
Data Science Salon: Adopting Machine Learning to Drive Revenue and Market ShareFormulatedby
The race is on to gain strategic and proprietary insights into changes in customer preferences before your competitors. This workshop will cover how and why machine learning is the tool for marketers to drive revenue and increase market share. The adoption of machine learning does not happen overnight. We will discuss the Five Es of machine learning maturity – Educating, Exploring, Engaging, Executing and Expanding. Hear real-world examples of using machine learning to accelerate revenue, identify new customers and introduce new products based on machine learning capabilities.
Next DSS MIA Event - https://datascience.salon/miami/
Data Science Salon: Data visualization and Analysis in the Florida Panthers H...Formulatedby
We will give an overview of how data visualization and data analysis are used within the Florida Panthers organization, around the National Hockey League, and in the sports industry in general, in a variety of different contexts. We discuss how analytics can be used to assist an NHL team’s front office, coaching staff, and scouting department. We also discuss the kinds of data we encounter on the business side of the organization in departments like sales and marketing, as well as the kinds of questions the league offices try to answer with the help of data.
Next DSS MIA Event - https://datascience.salon/miami/
Data Science Salon: Building a Data Science CultureFormulatedby
Catalina is a Data Scientist with a specialty in building out scalable data solutions for startups.
Next DSS MIA Event - https://datascience.salon/miami/
There's a huge hype around the power of data science across industries. However, not all companies have been able to successfully build out their data science capabilities, and some are just starting to think about doing so. Just as each business is unique, each data science endeavor is unique. In this talk, we explore both the non-negotiables in building a data science culture and how to tailor your data science initiatives to match your business needs at different stages of your journey towards reaping the benefits of a data science culture.
Data Science Salon: Digital Transformation: The Data Science CatalystFormulatedby
This document discusses how data science can catalyze digital transformation. It begins by defining data science and digital transformation, noting that digital transformation provides the foundation for data science enablement. Several challenges of digital transformation are outlined, including increasing competition, changing consumer behavior, and legacy technical and cultural issues. The presentation argues that data science can help address these challenges by leveraging customer data to personalize engagement across channels. Specific data science techniques are described, such as propensity modeling, content personalization, social media interaction analysis, text analysis, and image/video analysis. Current limitations of these approaches are acknowledged, and the document concludes by emphasizing the relationship between data science and digital transformation.
Data Science Salon: Quit Wasting Time – Case Studies in Production Machine Le...Formulatedby
Presented by Yashas Vaidya, Sr Data Scientist at DataIku
Next DSS MIA Event - https://datascience.salon/miami/
The steps to taking a machine learning model to production. Modern architectures and technologies for building production machine learning. An overview of the talent and processes for creating and maintaining production machine learning.
Data Science Salon: Enabling self-service predictive analytics at BidtellectFormulatedby
Having previously worked at both Millennial Media and AOL, Michael Conway brought his expertise to Bidtellect tasked with transforming the business to a self-service SaaS-based content distribution platform, enabling the company to grow 10-fold.
Next DSS MIA Event - https://datascience.salon/miami/
During the 30-minute presentation, Michael will provide background information about Bidtellect and how data is an integral component of the business managing their premium native inventory across their supply ecosystem with over 5 billion native auctions per day. As Bidtellect embraces big data, Michael will share the challenges and successes he and his team have experienced along the way. In addition, Steve Sarsfield, Vertica Senior Product Marketing Manager, will be available to discuss how specific technologies (SQL, Python, R and embedded algorithms) can be combined in an MPP environment to achieve big data analytics success.
Data Science Salon: MCL Clustering of Sparse GraphsFormulatedby
The increasing need for clustering in several scientific domains has inevitably driven the creation of innovative algorithms, each designed to perform more efficiently in certain applications. More specifically, in many applications the data entities involved can be portrayed effectively by a graph as a collection of nodes and edges. One of the most established algorithms for graph clustering problems is the Markov Cluster Algorithm (MCL).
Next DSS MIA Event - https://datascience.salon/miami/
When dealing with large and complex datasets, the underlying graphs can easily reach proportions that independent computing systems are inadequate to deal with. Additionally, the graphs encountered are typically sparse: the number of edges is far smaller than might be possible in a fully-connected graph. Consequently, there is a concrete need for algorithms that are designed to handle sparse graph clustering utilizing distributed computing resources.
Our motivation was the development of a distributed architecture, able to accommodate large and sparse graphs, to actualize the MCL and R-MCL algorithm. The Apache Spark framework was chosen due to its ability to utilize distributed resources and its proven track record. Although Spark is a framework capable of handling massive datasets, it currently does not provide rich support for computation with sparse matrices and sparse graphs. Hence, methods have been implemented to enable the exploitation of sparse adjacency matrices in distributed sparse matrix multiplication, a critical component of MCL. The proposed solution can handle arbitrarily large inputs, provide almost linear speed-up with the addition of computational resources and output results directly comparable to the non-distributed reference MCL implementation.
Data Science Salon: Applying Machine Learning to Modernize Business ProcessesFormulatedby
Next DSS MIA Event - https://datascience.salon/miami/
For most data scientist building models is hard work, but deploying them into production and impacting business processes can be even harder. In fact, research shows that only about 10% of data science models get deployed into production, and those that do can take between 6 to 9 months to be deployed. This session will highlight the challenges that data scientist and organizations alike face when trying to deploy machine learning models and how to overcome these challenges. It will examine several use cases where models built in R and Python have been able to deliver impactful results across several industries.
Data Science Salon: Deep Learning as a Product @ ScribdFormulatedby
Presented by Kevin Perko, Head of Data Science at Scribd
Next DSS NYC Event 👉 https://datascience.salon/newyork/
Next DSS LA Event 👉 https://datascience.salon/la/
Kevin will cover his experience using deep learning, going from scratch to deploying models in production to improve the product experience. He goes in-depth in terms of how we started deep learning from scratch, including navigating the maze of frameworks and hyper-parameters to optimize. Kevin will discuss pitfalls of using other people's algorithms and make a call for more rigor in publishing data science blog posts. Kevin closes with how his failure turned into an open source contribution and the work in moving from dev to production.
Data Science Salon: Building smart AI: How Deep Learning Can Get You Into Dee...Formulatedby
This document discusses building smart AI and the potential problems with deep learning. It notes that while machine learning and deep learning have advanced significantly, it is important not to lose sight of causality and transparency. Deep learning models can ignore causal relationships and reinforce biases if not developed properly. The document provides examples of using predictive analytics and machine learning responsibly in areas like recruiting, customer service chatbots, and summarizing key insights from chat data to improve agent performance. It emphasizes the need to formalize why certain approaches are taken and ensure models are designed to avoid potential harms.
Data Science Salon: The Age of Co-creationFormulatedby
Ann Greenberg gave a presentation on co-creation and the future of entertainment at a data science conference. She discussed how the current entertainment business model is broken and how moving from consumption to creation through tools like democratic cinema and growing stories rather than just telling them can help create new forms of storytelling. She also talked about how abundant data, smart algorithms, and powerful computing are enabling new possibilities and how entertainment AI can bridge human and machine creativity.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
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8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
2. OpenVax @ Mount Sinai
● www.openvax.org
● Focus: personalized cancer vaccines
○ Machine learning for immunology
○ Cancer genomics
● Started: January 1st, 2018
● Enthusiastically translational research
● Open source software: github.com/openvax
5. Immune system kills (most) cancer cells
Three E’s of cancer immunity, Ian York (2007)
6. Immune avoidance a hallmark of cancer
Hallmarks of
Cancer: The Next
Generation
(2011)
Don’t get eaten
by immune cells
7. Cancer immunotherapy
● Traditional treatments: focus on killing cancer cells directly
● Immunotherapy: get the immune system to kill the cancer
● Why is the immune system allowing cancer to spread?
○ Cancer cells inhibiting immune cells
■ Block the inhibitory signals!
○ Immune cells unable to recognize cancer as non-self
■ Teach the immune system what to kill
8. Flavors of cancer immunotherapy
Checkpoint blockade Cellular therapies Vaccines
Disinhibit CD8+ T-cells,
antigens responsible for
tumor clearance unknown.
Success stories:
● CTLA-4 (ipi)
● PD-1 (pembro, nivo)
● PD-L1 ( atezo)
Ex-vivo expansion of
patient T-cells after
receptor engineering
and/or selection.
Success stories:
● CD19 CAR T-cells for
B-cell malignancies
Therapeutic vaccines
against tumor antigens.
Significant interest in
personalized “neo-antigen”
vaccines.
Success stories:
● ???
● Hints of efficacy in
neoantigen vaccine trials
11. What’s in a therapeutic cancer vaccine?
● Tumor antigen
○ What should immune system look for?
● Adjuvant
○ Something the immune system already responds to as
dangerous
○ Examples: double-stranded RNA, mineral oil, dead
bacteria
● Objective: get the immune system to learn that the antigen is
bad and cells which have it should be killed
12. Tumor-specific antigens
● Don’t occur in normal
cells
○ most commonly:
mutated proteins
● Unlikely to be shared
between patients
● Called “neo-antigens”
Getting Personal with Neoantigen-Based Therapeutic Cancer Vaccines
13. Typical personalized cancer vaccine
pipeline
● Sequence DNA from tumor and
patient
○ Identify tumor-specific
mutations
● Sequence RNA from tumor
○ Which mutations are being
produced into proteins?
● Predict which mutations can be
seen by immune system Computational genomics tools for dissecting tumour–immune cell interactions
14. Murine Experiment
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens, Gubin et al. (2014)
● Taconic 129S6 mice
● MCA-T3 sarcoma cell line
● “mLama4” & “mAlg8” are
predicted neoantigens
● Long peptide vaccine +
Poly(I:C) adjuvant
15. More Mouse Evidence
Mutated neo-antigens as targets for individualized cancer immunotherapy (Figure 3.18), Vormehr (2016)
● BALB/c mice
● CT26 colon cell line
● mRNA vaccine
● Two groups of 5
epitopes (#2 works)
○ Individual
epitopes don’t
work
16. Cathy Wu & Pat Ott’s trial @ DFCI
● 6 (stage III & IV) melanoma patients
● Up to 20 mutated peptides per vaccine
● Adjuvant: Poly-ICLC
17. DFCI Trial: Tumor Control
Of six vaccinated patients, four had no recurrence
at 25 months after vaccination, while two with
recurrent disease were subsequently treated with
anti-PD-1 (anti-programmed cell death-1) therapy
and experienced complete tumour regression, with
expansion of the repertoire of neoantigen-specific T
cells.
19. DNA Sequencing
NextSeq 500 in Mount Sinai’s Sequencing Core
● Human genome ~= 3
billion nucleotides
○ Longest
chromosome ~=
250M nucleotides
● Split DNA into tiny
fragments
● Read billions of short
sequences
24. T cell surveillance
Yewdell, J.W., Reits, E. & Neefjes, J., 2003. Nature Reviews Immunology
● Proteins cleaved by proteasome
● Some of the resulting peptides
loaded onto MHC to be
presented on cell surface
● T cells perform surveillance of
these peptide/MHC complexes
● Abnormal (non-self) displayed
peptides lead to a cytotoxic T cell
response
24
25. MHC
● Thousands of MHC alleles in
human population
● Each allele capable of binding a
distinct set of peptides
● Objective: Predict whether an
MHC allele will bind a given
peptide
25
Holland, C.J., Cole, D.K. & Godkin, A., 2013. Frontiers in Immunology
26. Immune Epitope Database (IEDB)
● Public dataset of B and T cell
epitopes and related data curated
from the literature
● Includes >200,000 in vitro binding
affinity measurements of purified
MHC/peptides, which is the core
training data for MHC ligand
prediction tools
27. Linear models perform reasonably well
● Binding motifs (Sette 1989)
● Position specific scoring
matrices (Parker 1994)
● Ignore dependencies between
positions
Bjoern Peters
28. Neural networks do better:
NetMHCpan (2007)
● Standard tool to predict peptide/MHC binding affinity given: peptide
sequence and binding groove residues of MHC allele
29. PGV001: Safety and Immunogenicity
of Personalized Genomic Vaccine
(Phase I Clinical Trial at Mount Sinai)
Nina Bhardwaj
30. PGV-001 Trial
● H&N, NSCLC, Breast, Ovarian, Urothelial, SCC, MM
● Patients w/o evidence of residual or metastatic disease
● Vaccine:
○ 10 peptides (~25 amino acids)
○ Adjuvant: Poly-ICLC
○ 10 intracutaneous injections over 6 months
● Peptide selection:
○ Phase cancer mutations with germline variants using RNA reads
○ Add multiple MHC I binding predictions overlapping same mutation
○ Ranking: expression * MHC I affinity
32. Trial Status
● Open & enrolling
● 1 H&N patient treated
● 1 MM patient with manufactured peptides, will begin
treatment soon
● 4 patients with DNA/RNA sequencing data
33. New Trials in 2018
● PGV for Glioblastoma
○ + Novocure’s TTfields
○ PI: Adelia Hormigo
● PGV for Bladder Cancer
○ + ⍺PD-1
○ PI: Matt Galsky
35. Open Source Tools Developed for PGV
Available at github.com/openvax
varcode Python interface for VCFs, variant effect prediction
isovar Determine mutant coding sequence from RNA-seq
vaxrank Vaccine peptide selection (including manufacturability)
epidisco Turn-key workflow to generate vaccine peptide report from FASTQ inputs (runs
all bioinformatics tools)
ketrew Workflow engine used to run tools on Google Cloud, AWS, and traditional HPC
mhctools Standard interface to pMHC binding predictors
pyensembl Python interface to Ensembl reference genome annotations