Currently, popular targets include CD family, BCMA, HER2, TROP2, Tissue factor, Nectin-4, FRα, EGFR, etc. Here, we briefly introduce ADC targets in solid tumors and hematological tumors.
Trophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdfDoriaFang
The more popular targets in ADC drugs include HER2, TROP2, EGFR, CLDN18.2, c-Met, CD19, PSMA, Muc1, BCMA and PDL1. Here we will introduce a new ADC target trophoblast glycoprotein (TPBG).
ADC Drugs For Non-small Cell Lung Cancer.pdfDoriaFang
Despite the rapid progress of targeted therapy in the field of NSCLC (non-small cell lung cancer), there are still unmet needs. This article summarizes the latest progress in the targeted therapy of Her2, Her3 and Trop-2 in NSCLC.
Global antibody-drug-conjugate-adc-clinical-trial-reviewEchoHan4
As innovative next-generation immunotherapeutic agents, antibody-drug conjugates (ADCs) are being developed worldwide as a major strategy to combat cancer and other immunological disorders. With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/druglnk-custom-synthesis.htm
With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/platform.htm
Trophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdfDoriaFang
The more popular targets in ADC drugs include HER2, TROP2, EGFR, CLDN18.2, c-Met, CD19, PSMA, Muc1, BCMA and PDL1. Here we will introduce a new ADC target trophoblast glycoprotein (TPBG).
ADC Drugs For Non-small Cell Lung Cancer.pdfDoriaFang
Despite the rapid progress of targeted therapy in the field of NSCLC (non-small cell lung cancer), there are still unmet needs. This article summarizes the latest progress in the targeted therapy of Her2, Her3 and Trop-2 in NSCLC.
Global antibody-drug-conjugate-adc-clinical-trial-reviewEchoHan4
As innovative next-generation immunotherapeutic agents, antibody-drug conjugates (ADCs) are being developed worldwide as a major strategy to combat cancer and other immunological disorders. With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/druglnk-custom-synthesis.htm
With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/platform.htm
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.
New Oncology Trends ADCs, Bispecific Antibodies & CAR-T Cell.pdfDoriaFang
Scientists are turning their attention to more innovative therapeutic strategies, such as next-generation ADCs, bispecific antibodies and CAR-T cell therapies, etc. as cancer therapy.
Hydrogels Deliver CAR-T cells For Solid Tumor Treatment.pdfDoriaFang
In the treatment of solid tumors, CAR-T has not yet achieved substantial breakthroughs. Could hydrogel-loaded CAT-T cells bring CAR-T therapy one step closer to solid tumors?
Background : During the conference of ASCO 2015, there was no consensus about TIL role in beast cancer and no recommendations concerning the microscopic assessment of TIL. In fact, the patients could be put on anti-PD1 drugs without the necessity of highlighting PD1 positive cells by using immunohistochemistry. Nevertheless, many questions about the prognostic impact of TIL, the methods of assessment, the type of TIL to count remain unresolved. Material and Methods : We performed a review of the literature on the sites : Pubmed and Cochrane. We used the key-words : �TIL in cancer�; �TIL in breast cancer� and �prognostic impact of TIL in breast cancer�. Results : According to our inclusion and exclusion criteria, thirty eight articles were retained. Our review of the literature showed that assessing TIL in high grade tumors seem unnecessary. They seem available in intermediate graded tumors. In neo-adjuvant and adjuvant conditions, CD3+ lymphocytes seem to be correlated to a good response to chemotherapy. After a chemotherapy, quantification T reg lymphocytes CD4 + FOXP3+ seems helpful because the decrease of their number is correlated to a good prognosis. Conclusion : The role of TIL in breast cancer is clearly established. The mechanisms of immune escape induced to discovery of immune therapy. The role of the microscopic examination and the subtyping of TIL using immunohistochemistry hasn�t been clearly established. Through this review of the literature, we tried to establish a diagram highlighting the different subtypes of TIL to evaluate and their prognostic impact.
Suicide gene therapy is based on the delivery of a gene encoding a cytotoxic protein into tumor cells.
For this, there are two possible strategies:
1. Indirect gene therapy using enzyme-activated pro-drug, which allows the conversion of a pro-drug into a lethal drug into cells.
2. Direct gene therapy using a toxin gene, whose expression can change the stability of the cell membrane and reduce the viability of tumor cells, or correct mutated pro-apoptotic genes, generally tumor suppressor genes that in normal condition induce cell suicide.
paraphrase the review in your own wordsThe tumor suppressor PTEN .pdfarihantgiftgallery
paraphrase the review in your own words?
The tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10), is
a lipid phosphatase that converts phosphatidylinositol-3, 4, 5- triphosphate (PIP3) into
phosphatidylinositol (4, 5)- diphosphate (PIP2). PTEN is well-known as the most highly mutated
tumor suppressor gene in the p53-post era [66, 67]. Recently, three papers by Nadav Bar and
Rivka Dikstein, Linhua Liu and colleagues, and Laura Poliseno and colleagues, have
demonstrated that PTEN was a bona fide target of miR-22 in a small cohort of cancer cell lines
that are driven from breast cancer, cervical cancer, prostate cancer, and bronchial epithelial
cancer. These studies contradict a uniform role of miR-22, indicating that under certain
circumstances, miR-22 may function as an oncogene because of its antagonistic effects on tumor
suppressive PTEN signaling [26, 68, 69] (Fig. 3). Using various miRNA target prediction
programs and/or RNAhybrid program for evaluating the minimum free energy hybridization,
these three groups all found that miR-22-PTEN was a high scoring miRNA-target pair. Enforced
or reduced expression of miR-22 in human HEK293T, cervical cancer HeLa and breast cancer
MCF-7 cell lines (Nadav Bar and Rivka Dikstein), anti-benzo[a]pyrene-7, 8-diol-9, 10-epoxide
(anti-BPDE)-induced transformed human bronchial epithelial cancer cell line 16HBE-T (Linhua
Liu and colleagues) and prostate cancer cell line DU145 (Laura Poliseno and colleagues),
revealed that miR-22 negatively regulated PTEN protein expression. Intriguingly, an inverse
correlation between miR-22 and PTEN mRNA expression has been presented by Poliseno et al.,
while Liu et al. found that there was no change of PTEN mRNA expression regardless of miR-
22 levels. A similarly inverse association of miR-22 and J. Xiong PTEN protein levels was
observed in 16HBE-T and its parental normal cell line16HBE (Linhua Liu and colleagues), and
in several prostate cancer cell lines, prostate cell lines and a prostate tumor tissue microarray
(Laura Poliseno and colleagues). Furthermore, the mature levels of miR-22 were significantly
increased in these tumor cells versus their normal counterparts. In line with this result, a direct
correlation between miR-22 expression and phosphorylated AKT or between the expression of
miR- 22 and that of DICER was also identified by Laura Poliseno and colleagues. These three
groups all showed that an intact binding site at the 3’UTR of PTEN mRNA was required for
miR-22 targeting. Functional analyses showed that miR-22 could induce apoptosis, inhibited
colony formation and suppressed motility of bronchial epithelial cancer cells (Linhua Liu and
colleagues), and intrinsically promote prostate cancer cell growth and tumorigenesis in tumor-
bearing nude mice (Laura Poliseno and colleagues). Subsequently, the influence of miR-22 on
the downstream signaling of PTEN was tested. Bar et al. showed that miR-22 could stimulate
AKT activity, and i.
Cyclic Peptides Current Status & Future Prospects.pdfDoriaFang
Researchers have made unremitting efforts to optimize peptides in order to improve the bioavailability of peptide drugs. Cyclization of peptides is one of the methods to optimize peptides. Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics.
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdfDoriaFang
Summary of Antibody–Oligonucleotide Conjugates(AOCs) in Clinical Trials, including products from Avidity Biosciences, Dyne Therapeutics, Tallac Therapeutics and Denali Therapeutics.
More Related Content
Similar to Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdf
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.
New Oncology Trends ADCs, Bispecific Antibodies & CAR-T Cell.pdfDoriaFang
Scientists are turning their attention to more innovative therapeutic strategies, such as next-generation ADCs, bispecific antibodies and CAR-T cell therapies, etc. as cancer therapy.
Hydrogels Deliver CAR-T cells For Solid Tumor Treatment.pdfDoriaFang
In the treatment of solid tumors, CAR-T has not yet achieved substantial breakthroughs. Could hydrogel-loaded CAT-T cells bring CAR-T therapy one step closer to solid tumors?
Background : During the conference of ASCO 2015, there was no consensus about TIL role in beast cancer and no recommendations concerning the microscopic assessment of TIL. In fact, the patients could be put on anti-PD1 drugs without the necessity of highlighting PD1 positive cells by using immunohistochemistry. Nevertheless, many questions about the prognostic impact of TIL, the methods of assessment, the type of TIL to count remain unresolved. Material and Methods : We performed a review of the literature on the sites : Pubmed and Cochrane. We used the key-words : �TIL in cancer�; �TIL in breast cancer� and �prognostic impact of TIL in breast cancer�. Results : According to our inclusion and exclusion criteria, thirty eight articles were retained. Our review of the literature showed that assessing TIL in high grade tumors seem unnecessary. They seem available in intermediate graded tumors. In neo-adjuvant and adjuvant conditions, CD3+ lymphocytes seem to be correlated to a good response to chemotherapy. After a chemotherapy, quantification T reg lymphocytes CD4 + FOXP3+ seems helpful because the decrease of their number is correlated to a good prognosis. Conclusion : The role of TIL in breast cancer is clearly established. The mechanisms of immune escape induced to discovery of immune therapy. The role of the microscopic examination and the subtyping of TIL using immunohistochemistry hasn�t been clearly established. Through this review of the literature, we tried to establish a diagram highlighting the different subtypes of TIL to evaluate and their prognostic impact.
Suicide gene therapy is based on the delivery of a gene encoding a cytotoxic protein into tumor cells.
For this, there are two possible strategies:
1. Indirect gene therapy using enzyme-activated pro-drug, which allows the conversion of a pro-drug into a lethal drug into cells.
2. Direct gene therapy using a toxin gene, whose expression can change the stability of the cell membrane and reduce the viability of tumor cells, or correct mutated pro-apoptotic genes, generally tumor suppressor genes that in normal condition induce cell suicide.
paraphrase the review in your own wordsThe tumor suppressor PTEN .pdfarihantgiftgallery
paraphrase the review in your own words?
The tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10), is
a lipid phosphatase that converts phosphatidylinositol-3, 4, 5- triphosphate (PIP3) into
phosphatidylinositol (4, 5)- diphosphate (PIP2). PTEN is well-known as the most highly mutated
tumor suppressor gene in the p53-post era [66, 67]. Recently, three papers by Nadav Bar and
Rivka Dikstein, Linhua Liu and colleagues, and Laura Poliseno and colleagues, have
demonstrated that PTEN was a bona fide target of miR-22 in a small cohort of cancer cell lines
that are driven from breast cancer, cervical cancer, prostate cancer, and bronchial epithelial
cancer. These studies contradict a uniform role of miR-22, indicating that under certain
circumstances, miR-22 may function as an oncogene because of its antagonistic effects on tumor
suppressive PTEN signaling [26, 68, 69] (Fig. 3). Using various miRNA target prediction
programs and/or RNAhybrid program for evaluating the minimum free energy hybridization,
these three groups all found that miR-22-PTEN was a high scoring miRNA-target pair. Enforced
or reduced expression of miR-22 in human HEK293T, cervical cancer HeLa and breast cancer
MCF-7 cell lines (Nadav Bar and Rivka Dikstein), anti-benzo[a]pyrene-7, 8-diol-9, 10-epoxide
(anti-BPDE)-induced transformed human bronchial epithelial cancer cell line 16HBE-T (Linhua
Liu and colleagues) and prostate cancer cell line DU145 (Laura Poliseno and colleagues),
revealed that miR-22 negatively regulated PTEN protein expression. Intriguingly, an inverse
correlation between miR-22 and PTEN mRNA expression has been presented by Poliseno et al.,
while Liu et al. found that there was no change of PTEN mRNA expression regardless of miR-
22 levels. A similarly inverse association of miR-22 and J. Xiong PTEN protein levels was
observed in 16HBE-T and its parental normal cell line16HBE (Linhua Liu and colleagues), and
in several prostate cancer cell lines, prostate cell lines and a prostate tumor tissue microarray
(Laura Poliseno and colleagues). Furthermore, the mature levels of miR-22 were significantly
increased in these tumor cells versus their normal counterparts. In line with this result, a direct
correlation between miR-22 expression and phosphorylated AKT or between the expression of
miR- 22 and that of DICER was also identified by Laura Poliseno and colleagues. These three
groups all showed that an intact binding site at the 3’UTR of PTEN mRNA was required for
miR-22 targeting. Functional analyses showed that miR-22 could induce apoptosis, inhibited
colony formation and suppressed motility of bronchial epithelial cancer cells (Linhua Liu and
colleagues), and intrinsically promote prostate cancer cell growth and tumorigenesis in tumor-
bearing nude mice (Laura Poliseno and colleagues). Subsequently, the influence of miR-22 on
the downstream signaling of PTEN was tested. Bar et al. showed that miR-22 could stimulate
AKT activity, and i.
Similar to Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdf (20)
Cyclic Peptides Current Status & Future Prospects.pdfDoriaFang
Researchers have made unremitting efforts to optimize peptides in order to improve the bioavailability of peptide drugs. Cyclization of peptides is one of the methods to optimize peptides. Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics.
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdfDoriaFang
Summary of Antibody–Oligonucleotide Conjugates(AOCs) in Clinical Trials, including products from Avidity Biosciences, Dyne Therapeutics, Tallac Therapeutics and Denali Therapeutics.
Alzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdfDoriaFang
Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment. Here we introduce the development of AD drugs (Aducanumab, Lecanemab & Donanemab).
Summary of Targeted Protein Degradation in Clinical Trials.pdfDoriaFang
Summary of targeted protein degradation, such as PROTAC and molecular glues in clinical trials. PROTAC and molecular glues are the two main modes of TPD technology based on the UPS.
Cleavable Linkers Used In ADC Development.pdfDoriaFang
The linker used in ADC is divided into two types: cleavable linker and non-cleavable linker. This artile mainly introduced the cleavable linkers used in ADC development.
The Role of Four Lipid Components Of LNPs.pdfDoriaFang
LNP consists of four components: ionizable cationic lipids, phospholipids, cholesterol, and PEG lipids. Each component plays a key role in terms of LNP preparations.
Similar to HER2, Trop-2 is a new hot target for research. Trodelvy has been one of the products receiving much attention in recent years, and Dato-DXd from AstraZeneca/Daiichi Sankyo is also advancing rapidly.
DS-8201 (Enhertu) A Potential ADC Drug Targeting HER2.pdfDoriaFang
Enhertu (fam-Trastuzumab deruxtecan-nxki) is a HER2-targeting ADC drug jointly developed by AstraZeneca and Daiichi Sankyo, also known as DS-8201 or T-DXd.
List of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdfDoriaFang
What are the new anti-cancer drugs approved in the first half of the year? The new drugs approved covered a variety of solid tumors and blood tumor types.
Summary of Treatments for Multiple Myeloma.pdfDoriaFang
Currently, there are a variety of drugs available for multiple myeloma, including traditional cytotoxic drugs, immunomodulatory analogs, proteasome inhibitors, antibody-based drugs and CAR T-cell therapy.
PROTAC Delivery System Recent Research Advances.pdfDoriaFang
The combination of PROTAC and multifunctional delivery systems will open up new research directions in the field of TPD. Here we will introduce the combination of PROTAC and multifunctional delivery systems.
Aptamer-Drug Conjugate (ApDC) Current Research Progress.pdfDoriaFang
ADCs, PDCs, ISACs, SMDC and Aptamer-Drug Conjugate (ApDC) are the conjugated drugs currently being developed. Here we will introduce the current research progress and challenges of ApDC.
FRα Targeting ADCs for Ovarian cancer.pdfDoriaFang
This article introduces FRα targets and FRα ADCs in clinical trials. There is only one FRα targeting ADC for ovarian cancer - mirvetuximab soravtansine-gynx (Elahere) and a few in clinical trials.
VAT Registration Outlined In UAE: Benefits and Requirementsuae taxgpt
Vat Registration is a legal obligation for businesses meeting the threshold requirement, helping companies avoid fines and ramifications. Contact now!
https://viralsocialtrends.com/vat-registration-outlined-in-uae/
Improving profitability for small businessBen Wann
In this comprehensive presentation, we will explore strategies and practical tips for enhancing profitability in small businesses. Tailored to meet the unique challenges faced by small enterprises, this session covers various aspects that directly impact the bottom line. Attendees will learn how to optimize operational efficiency, manage expenses, and increase revenue through innovative marketing and customer engagement techniques.
RMD24 | Debunking the non-endemic revenue myth Marvin Vacquier Droop | First ...BBPMedia1
Marvin neemt je in deze presentatie mee in de voordelen van non-endemic advertising op retail media netwerken. Hij brengt ook de uitdagingen in beeld die de markt op dit moment heeft op het gebied van retail media voor niet-leveranciers.
Retail media wordt gezien als het nieuwe advertising-medium en ook mediabureaus richten massaal retail media-afdelingen op. Merken die niet in de betreffende winkel liggen staan ook nog niet in de rij om op de retail media netwerken te adverteren. Marvin belicht de uitdagingen die er zijn om echt aansluiting te vinden op die markt van non-endemic advertising.
Putting the SPARK into Virtual Training.pptxCynthia Clay
This 60-minute webinar, sponsored by Adobe, was delivered for the Training Mag Network. It explored the five elements of SPARK: Storytelling, Purpose, Action, Relationships, and Kudos. Knowing how to tell a well-structured story is key to building long-term memory. Stating a clear purpose that doesn't take away from the discovery learning process is critical. Ensuring that people move from theory to practical application is imperative. Creating strong social learning is the key to commitment and engagement. Validating and affirming participants' comments is the way to create a positive learning environment.
LA HUG - Video Testimonials with Chynna Morgan - June 2024Lital Barkan
Have you ever heard that user-generated content or video testimonials can take your brand to the next level? We will explore how you can effectively use video testimonials to leverage and boost your sales, content strategy, and increase your CRM data.🤯
We will dig deeper into:
1. How to capture video testimonials that convert from your audience 🎥
2. How to leverage your testimonials to boost your sales 💲
3. How you can capture more CRM data to understand your audience better through video testimonials. 📊
Digital Transformation and IT Strategy Toolkit and TemplatesAurelien Domont, MBA
This Digital Transformation and IT Strategy Toolkit was created by ex-McKinsey, Deloitte and BCG Management Consultants, after more than 5,000 hours of work. It is considered the world's best & most comprehensive Digital Transformation and IT Strategy Toolkit. It includes all the Frameworks, Best Practices & Templates required to successfully undertake the Digital Transformation of your organization and define a robust IT Strategy.
Editable Toolkit to help you reuse our content: 700 Powerpoint slides | 35 Excel sheets | 84 minutes of Video training
This PowerPoint presentation is only a small preview of our Toolkits. For more details, visit www.domontconsulting.com
RMD24 | Retail media: hoe zet je dit in als je geen AH of Unilever bent? Heid...BBPMedia1
Grote partijen zijn al een tijdje onderweg met retail media. Ondertussen worden in dit domein ook de kansen zichtbaar voor andere spelers in de markt. Maar met die kansen ontstaan ook vragen: Zelf retail media worden of erop adverteren? In welke fase van de funnel past het en hoe integreer je het in een mediaplan? Wat is nu precies het verschil met marketplaces en Programmatic ads? In dit half uur beslechten we de dilemma's en krijg je antwoorden op wanneer het voor jou tijd is om de volgende stap te zetten.
Discover the innovative and creative projects that highlight my journey throu...dylandmeas
Discover the innovative and creative projects that highlight my journey through Full Sail University. Below, you’ll find a collection of my work showcasing my skills and expertise in digital marketing, event planning, and media production.
Cracking the Workplace Discipline Code Main.pptxWorkforce Group
Cultivating and maintaining discipline within teams is a critical differentiator for successful organisations.
Forward-thinking leaders and business managers understand the impact that discipline has on organisational success. A disciplined workforce operates with clarity, focus, and a shared understanding of expectations, ultimately driving better results, optimising productivity, and facilitating seamless collaboration.
Although discipline is not a one-size-fits-all approach, it can help create a work environment that encourages personal growth and accountability rather than solely relying on punitive measures.
In this deck, you will learn the significance of workplace discipline for organisational success. You’ll also learn
• Four (4) workplace discipline methods you should consider
• The best and most practical approach to implementing workplace discipline.
• Three (3) key tips to maintain a disciplined workplace.
Kseniya Leshchenko: Shared development support service model as the way to ma...Lviv Startup Club
Kseniya Leshchenko: Shared development support service model as the way to make small projects with small budgets profitable for the company (UA)
Kyiv PMDay 2024 Summer
Website – www.pmday.org
Youtube – https://www.youtube.com/startuplviv
FB – https://www.facebook.com/pmdayconference
Implicitly or explicitly all competing businesses employ a strategy to select a mix
of marketing resources. Formulating such competitive strategies fundamentally
involves recognizing relationships between elements of the marketing mix (e.g.,
price and product quality), as well as assessing competitive and market conditions
(i.e., industry structure in the language of economics).
Attending a job Interview for B1 and B2 Englsih learnersErika906060
It is a sample of an interview for a business english class for pre-intermediate and intermediate english students with emphasis on the speking ability.
Attending a job Interview for B1 and B2 Englsih learners
Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdf
1. Biopharma PEG https://www.biochempeg.com
Summary of ADC Targets For Solid Tumors &
Hematological Tumors
The design concept of antibody-drug conjugate (ADC) has a long history. As early as
1913, Professor Paul Ehrlich, the father of chemotherapy and Nobel laureate, first
proposed the concept of "magic bullet". That is, cytotoxic drugs are installed on specific
monoclonal antibodies to achieve targeted killing of tumor cells. Currently available ADC
drugs are based on this theory. By connecting cytotoxic drugs to monoclonal antibodies,
monoclonal antibodies can be used as carriers to efficiently transport small molecule
cytotoxic drugs to the target tumor cells in a targeted manner.
Antibody-drug conjugates (ADCs) have developed rapidly in recent years, anti-tumor ADC
drugs are a class of targeted drugs with high attention. By the end of 2022, a total of 15
ADC drugs have been approved for marketing worldwide, and more than 140 are in
clinical trials. It is estimated that by 2030, the ADC market will exceed $15 billion.
ADC drugs are used as drug delivery vehicles due to the high target specificity and long
half-life of antibodies. Theoretically, by targeting monoclonal antibodies, ADCs can
precisely find the lesion and achieve a real " prescribe the right medicine ". Therefore, the
selection of the antibody target is very important. Target antigens should be highly
expressed in tumor tissues, but not expressed in normal tissues. Currently, popular
targets include CD family (CD33, CD30, CD22, CD79B, CD19), BCMA, HER2, TROP2,
Tissue factor (TF), Nectin-4, FRα, EGFR, etc. Here, we briefly introduce some ADC
targets in solid tumors and hematological tumors.
ADC Targets For Solid Tumors
To date, FDA-approved ADC targets for the treatment of solid tumors include HER2,
TROP2, Tissue factor (TF), Nectin-4, FRα, and EGFR.
2. Biopharma PEG https://www.biochempeg.com
Figure 1. ADC targets for solid tumors
(Source: References [1])
HER2
HER2 is a 185kda transmembrane glycoprotein belonging to the EGFR family.
Amplification of the HER2/neu gene is a known driver of human malignancy and
metastasis. HER2 has been a therapeutic target for decades because of its role in cancer.
HER2 has also been a target for ADCs, and both T-DM1 and T-DXT are approved for use
in patients with HER2-positive metastatic breast cancer.
There are several mechanisms of HER2 endocytosis. The first is CME.
Co-immunoprecipitation clearly shows that HER2 binds directly to AP-2. In addition,
dynasore can completely block HER2 endocytosis in SKBR3 cells. In addition, HER2 has
been shown to utilize the fossa mediated endocytosis pathway and the CLIC/GEEC
endocytosis pathway.
Currently, there are three ADC drugs targeting HER2 on the market, namely Kadcyla,
Enhertu, and RC48.
3. Biopharma PEG https://www.biochempeg.com
TROP-2
TROP-2 is a 46kDa monomeric glycoprotein with properties such as selective
overexpression, structural endocytosis, and directed lysosomal, making it a very attractive
target for ADCs. The internalization mechanism of Trop2 is related to CME.
In addition, Trop2 binds to a variety of ligands, such as claudin-1, claudin-7, cyclin D1, and
IGF1. However, none of these ligands have been shown to be internalized when binding
or interacting with Trop2. Therefore, Trop2 endocytosis is more intense in tumor cells than
in normal cells, suggesting that Trop2 is a good target for ADC.
TF (Tissue factor)
TF (Tissue factor), also known as thromboplastin factor III or CD142, is a transmembrane
glycoprotein with procoagulant activity that has the ability to induce intracellular signaling
in combination with proteolytic enzyme factor VIIa (FVIIa). TF is thought to promote
cancer progression through FVIA-dependent intracellular signaling pathways that regulate
cell survival, proliferation, metastasis, and angiogenesis. It is upregulated in various solid
tumors and tumor vascular systems due to hypoxia-induced signaling.
The internalized properties of this antigen are ideal for developing of TF-targeted ADCs. In
addition, a TF-FVIIa-mediated mechanism of induction of surface TF expression has been
reported, in which the formation of the TF-FVIIa complex leads to the release of TF from
the Golgi apparatus and then transport to the membrane, resulting in enhanced cell
surface TF expression. If this effect can be induced by anti-TF ADCs, then this could allow
repeated targeting of malignant cells expressing TF.
Nectin-4
Nectin-4 is a 66 kDa type I transmembrane protein whose primary role is to facilitate
intercellular contacts. Nectin-4 is attractive as an ADC target because it has been shown
to be overexpressed in several tumor types but barely present in normal adult tissues.
At present, there is no information has been found on endocytosis of natural ligands or
complexes of mAb/ADC and nectin-4, but the research on endocytosis of nectin-4
combined with pathogens can be used for reference. Nectin-4 is also a receptor for
measles virus, and studies have shown that measles virus enters MCF7, HTB-20 breast
cancer and DLD-1 colorectal cancer cells through macropinocytosis. Viral entry requires
PAK1, whereas the dynamin inhibitor Dynasore had no effect on viral entry. In addition,
cells expressing the dominant negative fossa protein did not eliminate the endocytosis of
the virus. Based on these indirect studies, nectin-4 exhibits the robust endocytosis
required by the viral receptor.
FRα
FRα (folate receptor alpha) is a membrane-bound metabolic folate receptor involved in
the intracellular transport of folate. Once bound to folate, the receptor-ligand complex is
4. Biopharma PEG https://www.biochempeg.com
internalized through a non-classical lipid raft endocytosis mechanism. FRα is highly
expressed in ovarian, breast, endometrial, mesothelioma, and lung cancers, but barely
expressed in normal cells, making this receptor well suited for ADC targeting.
Furthermore, FRα is thought to assist pro-tumor signaling by binding to folate, inducing
downstream effects such as activation of STAT3, intracellular transport of FRα as a
transcription factor as a growth pathway, and intracellular transport of folate for DNA
biosynthesis.
EGFR
Epidermal growth factor receptor (EGFR) belongs to the human epidermal growth factor
receptor family, which is highly expressed in a variety of solid tumors, and the signaling
pathway triggered by EGFR can cause tumor proliferation. Antibody-targeted drugs
against EGFR, ranging from monoclonal antibodies such as cetuximab and panitumumab,
to today's bispecific antibodies and ADC drugs, have significantly improved efficacy and
specificity.
The application of chimeric antibody cetuzumab in ADC drugs has been reported. In
addition, MAb806 is an IgG1 κtype monoclonal antibody targeting EGFRvIII (a
tumor-specific target that does not occur under normal physiological conditions), with
good specificity and internalization properties, and can be used as a small molecule drug
delivery vector.
ADC Targets For Hematological Tumors
For hematologic tumors, immune lineage-specific biomarkers such as CD19, CD20, CD22,
CD33, CD79B and BCMA are widely and uniformly expressed at high levels on malignant
blood cells, and thus have been extensively explored as candidate targets for ADC
development. In addition, the target antigens of approved ADCs are easily internalized
after binding, which is an important feature that contributes to the efficacy of ADCs.
5. Biopharma PEG https://www.biochempeg.com
Figure 2. ADC targets for hematological tumors
(Source: References [1])
CD19
CD19 is considered to be a pan-B cell marker and a major signaling component of
multimolecular complexes on the surface of mature B cells. The expression of CD19 is
highly conserved in most B-cell malignancies, and in addition, CD19 has rapid
internalization kinetics and does not shed into circulation, making it an ideal ADC target
antigen.
CD22
CD22 is a 140 kDa transmembrane glycoprotein that, like CD33, is a member of the
Siglec family and shares several structural features with the family. The key difference is
that CD22 is much larger than CD33 because it has multiple Ig domains and ITIM/
6. Biopharma PEG https://www.biochempeg.com
ITIM-like motifs. Expression of CD22 is limited to B cells, and CD22 is expressed at
elevated levels in most mother cells of a variety of B-cell malignancies, including ALL.
CD22 is endocytized by the CME. Native-like ligands accumulate intracellularly through
constitutive rapid endocytosis of CD22. These ligands are sorted for degradation in
lysosomes, while CD22 is recycled back to the cell surface. In addition, CD22
ligand-induced endocytosis activates intracellular pools that replenish or increase the
expression levels of CD22 on the cell surface. Therefore, CD22 has favorable endocytic
properties for ADCs.
CD30
CD30 is a 120kda transmembrane glycoprotein belonging to the tumor necrosis factor
receptor (TNFR) superfamily. Its extracellular portion consists of six cysteine-rich domains
(CRDs) in an extended conformation. CD30 is expressed on activated T cells and B cells,
as well as various lymphoid neoplasms, including Hodgkin lymphoma and ALCL.
CD30 is not endocytotic, instead, it is shed by proteolytic cleavage, and the shedding of
CD30 is mediated by matrix metalloproteinases (MMPs). Shedding is a feature of CD30
biology, and high concentrations of circulating soluble CD30 can be used as a serum
marker to monitor tumor progression. For the efficacy of ADCs, elevated CD30 circulating
levels appear to isolate injected ADCs, thereby reducing the number of ADCs able to
target CD30-positive tumor sites. Therefore, the lack of endocytosis suggests that CD30
is not an ideal ADC target.
CD33
CD33, a 67kda transmembrane glycoprotein receptor, is a member of the sialic-binding
immunoglobulin-like lectin (SIGLEC) family, which is normally expressed on normal
myeloid cells and is the target of Gemtuzumab ozogamicin due to its preferential
overexpression on AML cells. The immunoreceptor tyrosine-based inhibitory motif (ITIM)
of CD33 regulates CD33 endocytosis, which can be activated by clathrin-mediated
endocytosis (CME). Regarding endocytosis efficiency, there was no correlation between
the expression level of CD33 in AML cells and its endocytosis rate. CD33 is a slowly
internalized antigen, and CD33 cross-linking does not improve endocytosis. AML patients
who do not respond to GO may be related to poor function of CD33 receptor ingestion.
CD79b
CD79b is expressed only in immature and mature B cells and is overexpressed in ≥80% of
B cells in malignant tumors. CD79a and CD79b are two non-covalently bound
transmembrane proteins that mediate signaling and endocytosis. For the latter, the
CD79a-CD79b heterodimer is a scaffold that controls BCR endocytosis. The endocytosis
of BCR is mainly accomplished by CME and mediated by AP-2. Interestingly, CD79a
directly interacts with the μ-subunit of AP-2, which in turn activates CD79b and leads to
endocytosis of the entire BCR complex.
7. Biopharma PEG https://www.biochempeg.com
In addition, for ADCs, CD79a can be internalized as a monomer, but CD79b cannot. If the
proximal membrane tyrosine (Y195) of CD79b is mutated, the binding of AP-2 to CD79a is
blocked, and endocytosis is also blocked. In 18% of activated B-cell-like DLBCL
specimens, Y195 was mutated. In summary, there is evidence that CD79b's endocytosis
depends on the internalization of the entire BCR complex, rather than as a monomer.
BCMA
BCMA or CD269, also known as TNFR superfamily member 17, transduces signals that
induce B cell survival and proliferation. BCMA has a molecular weight of only 20.2 kDa,
and its ligand-bound extracellular region has an "arm-chair" conformation, consisting of
six CRDS. In addition to multiple myeloma, BCMA is also expressed in many
hematological malignancies such as Hodgkin's lymphoma and non-Hodgkin's lymphoma.
However, little is known about the precise endocytic pathway utilized by BCMA. Related to
endocytosis, sialylation is a regulatory function that may induce BCMA to endocytosis
using CME.
Conclusion
At present, 15 ADC drugs have been approved for marketing in the world, and more than
450 ADC drugs are in different stages of research and development. From the perspective
of the target distribution of ADC products, HER2 is the most popular target for ADC
research and development, followed by TROP2. The competition for ADC drugs is
increasing. If pharmaceutical companies want to stand out, the selection of targets is the
key.
In recent years, the development of ADCs has also exploded as improvements have been
made through better selection of cytotoxic drugs, bioconjugation methods, better targeting
of antigens, and optimized antibody engineering. In 2022 alone, 249 clinical trials
evaluating ADCs have been initiated, a 35% increase compared to 2021, and there is
significant overlap in the tumor targets being studied. In the future, ADC drugs will have a
huge potential in the anti-tumor market. On this track, if a company wants to stand out, a
differentiated layout that meets clinical needs is the key, especially in the selection of
targets, which determines the company's position in the future commercial competition.
Biopharma PEG, a professional PEG derivatives supplier, is dedicated to manufacturing
and supplying high purity ADC linkers to our clients all over the world. We offer the full
range of PEG derivative development services and provide the most comprehensive
media for conjugation research.
References:
[1].Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug
Conjugates (ADCs) in Haematopoietic and Solid Cancers. Cancers (Basel).2023 Mar;
8. Biopharma PEG https://www.biochempeg.com
15(6): 1845.
[2]. Impact of EndocytosisMechanisms for the Receptors Targeted by the Currently
Approved Antibody-DrugConjugates (ADCs)—A Necessity for Future ADC Research and
Development. Pharmaceuticals(Basel). 2021 Jul; 14(7): 674.
Related articles:
[1]. Summary of Approved HER2 ADCs on The Market & in Clinical Trials
[2]. Overview of HER2-targeted Drugs
[3]. Clinical Development of ADC Drugs Targeting TROP-2
[4]. The Rise of the TROP2-Directed ADCs for Solid Tumors
[5]. FDA Approves Tivdak - First Tissue Factor (TF)-Targeted Antibody Conjugate Drug
(ADC)
[6]. Nectin-4-Directed Drugs for Solid Tumors
[7]. Novel FRα-targeting Antibody-drug Conjugates (ADCs)
[8]. EGFR-Directed ADCs for Cancer Treatment