T cells genetically engineered to express chimeric antigen receptors (CAR) have proven an impressive therapeutic activity in patients with certain subtypes of B cell leukaemia or lymphoma, with promising efficacy also demonstrated in patients with multiple myeloma. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. Key challenges relating to CAR T cells include the lack of tumor exclusive target, restricted CAR-T cell trafficking to tumor sites, antigen escape and heterogeneity as well as a highly immunosuppressive microenvironment. In this report, we review the current state of the CAR-T technologies as a clinical treatment in solid tumor and we highlight the preclinical innovative designs of novel CAR T cell products that are being developed to increase and expand the clinical benefits of these treatments in patients with solid malignancies.
T cells genetically engineered to express chimeric antigen receptors (CAR) have proven an impressive therapeutic activity in patients with certain subtypes of B cell leukaemia or lymphoma, with promising efficacy also demonstrated in patients with multiple myeloma. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. Key challenges relating to CAR T cells include the lack of tumor exclusive target, restricted CAR-T cell trafficking to tumor sites, antigen escape and heterogeneity as well as a highly immunosuppressive microenvironment. In this report, we review the current state of the CAR-T technologies as a clinical treatment in solid tumor and we highlight the preclinical innovative designs of novel CAR T cell products that are being developed to increase and expand the clinical benefits of these treatments in patients with solid malignancies.
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
Immuno-Oncology: An Evolving Approach to Cancer Care
Review a downloadable slide deck by Thomas F. Gajewski, MD, PhD, covering the most clinically relevant new data reported from Immuno-Oncology: An Evolving Approach to Cancer Care.
Target Audience
This activity is designed to meet the educational needs of oncologists and other healthcare professionals involved in cancer care.
Format: Microsoft PowerPoint (.ppt) | File size: 26.2 MB | Date posted: 6/20/2012
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of June 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CE provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
Immunological Disorders can be classified into 3 distinct categories.They are Hypersensitivity, Autoimmunity and Immunodeficiency.Here in this presentation we talk about Immunodeficiency disorders.Get more on our blog : http://dentistryandmedicine.blogspot.com/
Graft versus host disease (GVHD) is an immune mediated disease due to complex interaction between donor (lymphoid tissue) and recipient’s immunity occurring after transplantation.
Two types
Acute (less than 100 days)
Chronic (more than 100 days)
By Dr. Usama Ragab Youssif
Definitions & Nomenclatures
Structure of immunoglobulins
Immunoglobulins in our bodies
Physiologic actions of immunoglobulins
The Idea behind use of immunoglobulins
Uses: indications, mechanisms, preparation, posology, administration
Adverse effects
Safe practice
Final bottom-line
Optimizing Treatment Sequencing for Patients With Relapsed/ Refractory Multi...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Shaji Kumar, MD, Professor of Hematological Malignancies
Mayo Clinic Cancer Center, offers expert insight on the assessment of MM, emerging and current therapies, cutting edge approaches to personalized treatments plans, and much more.
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
Immuno-Oncology: An Evolving Approach to Cancer Care
Review a downloadable slide deck by Thomas F. Gajewski, MD, PhD, covering the most clinically relevant new data reported from Immuno-Oncology: An Evolving Approach to Cancer Care.
Target Audience
This activity is designed to meet the educational needs of oncologists and other healthcare professionals involved in cancer care.
Format: Microsoft PowerPoint (.ppt) | File size: 26.2 MB | Date posted: 6/20/2012
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of June 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CE provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
Immunological Disorders can be classified into 3 distinct categories.They are Hypersensitivity, Autoimmunity and Immunodeficiency.Here in this presentation we talk about Immunodeficiency disorders.Get more on our blog : http://dentistryandmedicine.blogspot.com/
Graft versus host disease (GVHD) is an immune mediated disease due to complex interaction between donor (lymphoid tissue) and recipient’s immunity occurring after transplantation.
Two types
Acute (less than 100 days)
Chronic (more than 100 days)
By Dr. Usama Ragab Youssif
Definitions & Nomenclatures
Structure of immunoglobulins
Immunoglobulins in our bodies
Physiologic actions of immunoglobulins
The Idea behind use of immunoglobulins
Uses: indications, mechanisms, preparation, posology, administration
Adverse effects
Safe practice
Final bottom-line
Optimizing Treatment Sequencing for Patients With Relapsed/ Refractory Multi...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Shaji Kumar, MD, Professor of Hematological Malignancies
Mayo Clinic Cancer Center, offers expert insight on the assessment of MM, emerging and current therapies, cutting edge approaches to personalized treatments plans, and much more.
Recent advancement in prevention and management of GVHD.pptxroysudip900
advances in prevention of GVHD by different investigational and approved methods of graft modulating, drugs, chemotherapy, analysis of published data, improved survival, future direction. different sources of stem cell and strategies to prevent mortality and morbidity
Clinical composition of the new EAU NMIBC prognostic factor risk groups based on the WHO 2004/2016 or the WHO 1973 grading classification systems
Additional clinical risk factors are:
age > 70;
multiple papillary tumours;
tumour diameter > 3 cm.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
New Strategies for the Prevention and Treatment of Graft vs. Host Disease (GVHD)
1. New Strategies for the
Prevention and Treatment of
Graft vs. Host Disease (GVHD)
Simrit Parmar, MD
Stem Cell Transplant & Cellular Therapy
BTG2013, Hong Kong
2. Risk Factors for Acute GVHD
• HLA disparity
• Increasing age
• Donor and recipient gender disparity
• Type and status of underlying disease
• Amount of radiation and intensity of the
transplant conditioning regimen
• Doses of methotrexate and cyclosporine or
tacrolimus
4. Acute GVHD
• Acute GVHD
– Typically occurs around the time of engraftment.
– Previously mis-defined as GVHD which occurs prior to day
100 post-transplant.
– Three main organs involved:
• Skin: macularpapular rash
• GI system: Nausea / Vomiting and Diarrhea
• Liver Abnormalities: typically cholestatic (jaundice).
– Incidence of 9-50% of sib transplants.
Vigorito et al. Blood 2009
5.
6.
7. Acute GVHD: Survival and Relapse
• Grade 0 acute GVHD — hazard ratio (HR) for TRM: 1.0
• Grade I — HR 1.5 (95% CI 1.2-2.0)
• Grade II — HR 2.5 (95% CI 2.0-3.1)
• Grade III — HR 5.8 (95% CI 4.4-7.5)
• Grade IV — HR 14.7 (95% CI 11-20)
• Grade 0 acute GVHD — hazard ratio (HR) for relapse 1.0
• Grade I — HR 0.94 (95% CI 0.8-1.2)
• Grade II — HR 0.60 (95% CI 0.5-0.8)
• Grade III — HR 0.48 (95% CI 0.3-0.8)
• Grade IV — HR 0.14 (95% CI 0.02-0.99)
D
E
A
T
H
R
E
L
A
P
S
E
8. “Be good or I’ll send you to
transplant”
“”I am telling you, by the time
they get done with you, you’ll be
wearing diapers”
“Do you want a
little vidaza or
total body skin
sloughing?”
11. Immune Function in HCT
• Dysfunctional immune responses are common in
clinical medicine
• Major mechanism of disease control due to GVT
reactions, yet major limitation of allogeneic HCT is
GVHD
• Controlling GVHD could lead to use of allogeneic
HCT in other clinical settings such as treatment of
autoimmune diseases and tolerance induction for
organ transplantation
12. Risk of GVHD in Two Eras
Gooley et al. N. Engl. J Med 363:2091, 2010
13. In vivo tracking of
light emitting donor cells
Allogeneic HCT
B
T
M
BM BM
BM
B
T
Bone Marrow
Splenocytes
FVB/N
WT
luc+
Balb/c
H-2q/Thy1.1H-2d/Thy1.2
CD4+
CD8+
B220+
NK1.1+
Gr-1/Mac-1+
2x105 cells/well Absolute light
emission
0.00 0.05 0.10 0.15
Luciferase 2A eGFPAct
luc+ reporter mouse
16. Approaches to the Prevention of GVHD
• Pharmacologic
– CNI/MTX
– CNI/MTX vs Rapa/MTX
• Graft source
– BM vs PBPC
– MRD vs URD vs UCB
• T Cell depletion
– CD34 Selection
– ATG, Campath
• Immune regulation
17. Regulation of Immune Function
• Critically important in health and disease
• Compartmentalization of immune
responses
• Cytokines
• Regulatory T cells (Treg, NK-T, iTreg, others)
RegulationReactivity
T regulatory cellT effector cell
CD4+ T Cell Subsets
18. CD4+CD25+ Regulatory T Cells
• Major population of cells which regulate immune
reactions
• Express transcription factor FoxP3
• Deficiency or mutation of FoxP3 has autoimmune
consequences in animal models and humans
• Cell contact-dependent suppression of alloreactive
responses in mixed lymphocyte reactions (MLR)
• Prevent organ specific autoimmune diseases in animal
models (e.g. IBD, diabetes)
• IL-10 and TGF- implicated in mediating suppressive
effect in vivo
19. Regulatory T-cells
• Allogeneic HCT recipients with aGVHD had Treg
frequencies 40% less than those without aGVHD.
• Treg frequencies decreased linearly with acute
GVHD severity.
• The frequency of Tregs at acute GVHD onset
predicted response to therapy.
Magenau et al. BBMT. 2010.
20. Magenau et al. BBMT. 2010.
38%
63%
Circulating Tregs predict OS
21. d15 Death from
GVHD
100
5000
1000
20000
1
10
100
1000
10000
0 20 40 60 0 20 40 600 20 40 60
Time [d] post BMT
RelativeSignalIntensity
0
25
50
75
100
0 20 40 60
Time [d] post BMT
Survival[%]
TCD BM only, n = 14
TCD BM + Tcon, n = 15
TCD BM + Tcon + Treg n = 9
Control of GVHD with Retention of GVL
TconBM only Tcon + Treg
500
5000
d5
Edinger et al. Nature Medicine 9:1144, 2003
22. Challenges for Clinical Translation of Treg
• Treg are rare cell populations
• Paucity of unique markers for isolation and
availability of clinical grade reagents
• Marginal functional assays in humans
• Regulatory requirements
32. Next Step: Adoptive Therapy with Treg
Day
-8
Day
-7
Day
-6
Day
-5
Day
-4
Day
-3
Day
-2
Day-
1 0 +1 +2
Day
+3
Day
+4
Day
+6
BU
Test
Dose
32mg/m2
Rest BU BU BU BU BMT Infusion
of
Ex-vivo
Expanded
Tregs
FLU
40
mg/m
2
FLU
40
mg/
m2
FLU
40
mg/
m2
FLU
40
mg/
m2
CY**
50
mg/k
g
CY**
50
mg/k
g
Day
-6
Day
-5
Day
-4
Day
-3
Day
-2
Day-1
0
MEL BU BU BU Infusion of
Ex-vivo
Expanded
Tregs
BMT
FLU
40
mg/m2
FLU
40
mg/m2
FLU
40
mg/m2
FLU
40
mg/m2
MMF+Sirolimus
41. Outcomes – U. of Perugia
Event-Free Survival
12/26 (46%)
• Regimen Related Toxicities:
– Veno-occlusive disease (3)
– Multi-organ failure (1)
• Acute GVHD grade III-IV (2)
• Serious infections (7)
• Relapse (AML 1)
Median follow-up 18.5 months
(range 16.1-27.6)
D’Ianni et al. Blood 2011
42. Conclusions
• GVHD remains the most significant
complication following allogeneic HCT
• Murine studies have demonstrated that
immune regulatory mechanisms play a
significant role in controlling dysfunctional
immune responses including GVHD
• Clinical translation is ongoing with promising
early results
