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Really good analysis and summary of the exciting field of TCRm. Together we are unlocking the potential of the human immune system with engineered soluble proteins! In 20 years there will be just as many TCRms in the clinic are their are antibodies today.

Insight review, findings and directions: Cancer therapy with antibodies Current treatments for most of solid cancers: combination therapy with target therapy; radiation, inhibitors, monoclonal antibodies, ADC - neoadjuvant therapy… nano antibodies… The greatest challenge in cancer therapy is to eradicate cancer cells with minimal damage to normal cells. Targeted therapy has been developed to meet that challenge, showing a substantially increased therapeutic index compared with conventional cancer therapies. Antibodies are important members of the family of targeted therapeutic agents because of their extraordinarily high specificity to the target antigens. Therapeutic antibodies use a range of mechanisms that directly or indirectly kill the cancer cells. Early antibodies were developed to directly antagonize targets on cancer cells. This was followed by advancements in linker technologies that allowed the production of antibody–drug conjugates (ADCs) that guide cytotoxic payloads to the cancer cells. Improvement in our understanding of the biology of T cells led to the production of immune checkpoint-inhibiting antibodies that indirectly kill the cancer cells through activation of the T cells. Even more recently, bispecific antibodies were synthetically designed to redirect the T cells of a patient to kill the cancer cells.

Enhertu: A New Era of Targeted Cancer Treatment with Room for Growth Traditionally, cancer treatment targeted specific types of tumors based on their location (e.g., breast cancer, lung cancer). However, a new drug called Enhertu is changing the game. It's the first antibody-drug conjugate (ADC) approved by the US FDA to treat cancers based on a shared molecular feature, HER2, rather than their origin. What is Enhertu and how does it work? Imagine a guided missile. Enhertu is like that, but for cancer cells. It has two key components: 1. Targeting antibody: This part recognizes and attaches to the HER2 protein found on the surface of many cancer cells. 2. Cell-killing payload: Once attached, Enhertu releases a potent drug that kills the cancer cell. Why is this a big deal? Enhertu's "pan-tumor" approval signifies a shift towards a more targeted approach to cancer treatment. It's effective against a range of HER2-positive cancers, including breast, lung, and stomach cancers. This personalized approach offers hope for better treatment outcomes for many patients. Are there any limitations? While Enhertu is a breakthrough, there's room for improvement. The "linker" that connects the antibody to the payload can be unstable, potentially causing side effects. Researchers are actively developing more stable linkers to address this. What's the future of ADCs? The success of Enhertu has sparked a surge in interest in ADCs. Pharmaceutical companies are investing heavily in this field. Interestingly, the possibilities go beyond just killing cancer cells. Scientists are exploring attaching other types of payloads to antibodies, such as immune modulators to boost the body's own defenses against cancer. Overall, Enhertu represents a significant step forward in personalized cancer treatment. With ongoing research to improve linker technology and explore new payloads, ADCs hold immense promise for the future of cancer therapy. #medicalaffairs #clinicaldevelopment #medicaljobs #clinicaljobs https://lnkd.in/efrtTQTh

📃Scientific paper: Peptide G-Protein-Coupled Receptors and ErbB Receptor Tyrosine Kinases in Cancer Abstract: SIMPLE SUMMARY: Cancer growth is regulated by receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs). The epidermal growth factor receptor (EGFR) is an RTK that binds ligands and causes tyrosine phosphorylation of protein substrates. Alternatively, the EGFR can tyrosine itself, leading to the activation of the ERK pathway, increasing cellular proliferation. The EGFR is mutated in several lung cancer patients, and these patients can be treated with tyrosine kinase inhibitors. The neurotensin receptor (NTSR1) is a GPCR, which binds peptides and alters signal transduction. Adding neurotensin to lung cancer cells increases phosphatidylinositol turnover, resulting in elevating cytosolic Ca(2+) and activating protein kinase C. SR48692 is an NTSR1 antagonist, which inhibits lung cancer proliferation. RTKs and GPCRs can act independently to alter cancer growth; however, NTSR1 regulates the tyrosine phosphorylation of RTKs such as the EGFR. RTKs and GPCRs interact to increase cancer proliferation. ABSTRACT: The ErbB RTKs (EGFR, HER2, HER3, and HER4) have been well-studied in cancer. EGFR, HER2, and HER3 stimulate cancer proliferation, principally by activating the phosphatidylinositol-3-kinase and extracellular signal-regulated kinase (ERK) pathways, resulting in increased cancer cell survival and proliferation. Cancer cells have high densities of the EGFR, HER2, and HER3 causing phosphorylation of tyrosine amino acids on protein substrates and tyrosine a... Continued on ES/IODE ➡️ https://etcse.fr/NZpVX ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Review Article Cancer therapy with antibodies Suman Paul, Maximilian F. Konig, Drew M. Pardoll, Chetan Bettegowda, Nickolas Papadopoulos, Katharine M. Wright, Sandra B. Gabelli, Mitchell Ho, Andrea van Elsas & Shibin Zhou  Nature Reviews Cancer volume 24, pages 399–426 (2024) https://lnkd.in/gDZE2tMG Abstract: The greatest challenge in cancer therapy is to eradicate cancer cells with minimal damage to normal cells. Targeted therapy has been developed to meet that challenge, showing a substantially increased therapeutic index compared with conventional cancer therapies. Antibodies are important members of the family of targeted therapeutic agents because of their extraordinarily high specificity to the target antigens. Therapeutic antibodies use a range of mechanisms that directly or indirectly kill the cancer cells. Early antibodies were developed to directly antagonize targets on cancer cells. This was followed by advancements in linker technologies that allowed the production of antibody–drug conjugates (ADCs) that guide cytotoxic payloads to the cancer cells. Improvement in our understanding of the biology of T cells led to the production of immune checkpoint-inhibiting antibodies that indirectly kill the cancer cells through activation of the T cells. Even more recently, bispecific antibodies were synthetically designed to redirect the T cells of a patient to kill the cancer cells. In this Review, we summarize the different approaches used by therapeutic antibodies to target cancer cells. We discuss their mechanisms of action, the structural basis for target specificity, clinical applications and the ongoing research to improve efficacy and reduce toxicity.

🔬𝐏𝐞𝐫𝐬𝐨𝐧𝐚𝐥𝐢𝐳𝐞𝐝 𝐜𝐚𝐧𝐜𝐞𝐫 𝐦𝐞𝐝𝐢𝐜𝐢𝐧𝐞: 𝐅𝐢𝐱𝐕𝐚𝐜 𝐩𝐥𝐚𝐭𝐟𝐨𝐫𝐦 𝐫𝐞𝐚𝐜𝐡𝐞𝐬 𝐦𝐢𝐥𝐞𝐬𝐭𝐨𝐧𝐞 𝐢𝐧 𝐦𝐞𝐥𝐚𝐧𝐨𝐦𝐚 𝐭𝐫𝐢𝐚𝐥 At BioNTech, we envisioned personalized cancer medicine over 20 years ago and have started to develop novel precision tools. #mRNA is still today one of the center pieces in our toolbox that our researchers pioneered. Our goal remains unchanged: We want to establish mRNA as a new class of therapeutics to help address treatment challenges in oncology. 𝐓𝐨𝐝𝐚𝐲, 𝐰𝐞 𝐚𝐫𝐞 𝐚 𝐬𝐭𝐞𝐩 𝐜𝐥𝐨𝐬𝐞𝐫 𝐭𝐨 𝐚𝐜𝐡𝐢𝐞𝐯𝐢𝐧𝐠 𝐨𝐮𝐫 𝐯𝐢𝐬𝐢𝐨𝐧. Our personalized mRNA cancer treatment candidate BNT111, which is based on our FixVac platform, met its primary endpoint in combination with the PD-1 checkpoint inhibitor cemiplimab, developed by our partner Regeneron, in a randomized Phase 2 trial. The data demonstrated a statistically significant improvement in overall response rate in patients with advanced, hard-to-treat #melanoma. The #FixVac platform is one of our proprietary key mRNA cancer vaccine platforms, which is designed to target specific cancer indications by encoding a fixed set of antigens. They were identified to be frequently expressed on tumors of the same type – in this case BNT111 encodes four melanoma-associated antigens. The aim of our FixVac approach is to provide a personalized indication-specific, off-the-shelf therapy for cancer patients, particularly those with advanced, hard-to-treat disease where the medical need is still high in various indications.

Indapta Therapeutics Secures $22.5 Million to Advance Clinical Trials of Innovative Cancer and Autoimmune Treatments “This funding will enable us to generate significant additional data in our ongoing trial of IDP-023 in cancer as well as initial data from our first trial in autoimmune disease” une disease” Post this "This funding will enable us to generate significant additional data in our ongoing trial of IDP-023 in cancer as well as initial data from our first trial in autoimmune disease," said Mark Frohlich, Indapta’s CEO. "Preliminary results of IDP-023 in cancer are encouraging and we look forward to initiating our Phase 1 trial for multiple sclerosis in Q1 2025. This financing, together with our recently announced collaboration with Sanofi, highlights the promise of our differentiated platform.” Advancing Clinical Trials of Lead Product IDP-023 Indapta has completed enrollment in the safety run-in portion of the Phase 1 clinical trial of IDP-023 in Non-Hodgkin’s Lymphoma (NHL) and Multiple Myeloma (MM), in which patients received up to three doses of IDP-023 without and with interleukin (IL)-2. As presented at the Society for Immunotherapy of Cancer meeting, the mean maximum decrease in serum M-protein or light chain was 73% in responding myeloma patients with relapsed/refractory disease, with three patients achieving a reduction of 84% or greater. Enrollment of cohorts receiving IDP-023 in combination with monoclonal antibodies targeting CD20 or CD38 is underway. In August, Indapta announced FDA clearance of its IND of IDP-023 in combination with ocrelizumab in progressive MS. The company’s approach is highly differentiated from other cellular approaches to autoimmune diseases, with at least three different mechanisms that can address the biology of the disease: 1) by combining with a B cell targeting antibody like ocrelizumab, IDP-023 can deplete B cells more effectively than antibody alone; 2) g-NK cells are capable of targeting autoreactive T and B cells that are known to upregulate HLA-E; and 3) given their inherent anti-viral activity, g-NK cells can potentially address the EBV viral reservoir that contributes to the disease pathogenesis. https://lnkd.in/eZDmbgWW

Happy Friday all! Check out this Nature Reviews Cancer article by Paul et al., "Cancer therapy with antibodies." Abstract: The greatest challenge in cancer therapy is to eradicate cancer cells with minimal damage to normal cells. Targeted therapy has been developed to meet that challenge, showing a substantially increased therapeutic index compared with conventional cancer therapies. Antibodies are important members of the family of targeted therapeutic agents because of their extraordinarily high specificity to the target antigens. Therapeutic antibodies use a range of mechanisms that directly or indirectly kill the cancer cells. Early antibodies were developed to directly antagonize targets on cancer cells. This was followed by advancements in linker technologies that allowed the production of antibody–drug conjugates (ADCs) that guide cytotoxic payloads to the cancer cells. Improvement in our understanding of the biology of T cells led to the production of immune checkpoint-inhibiting antibodies that indirectly kill the cancer cells through activation of the T cells. Even more recently, bispecific antibodies were synthetically designed to redirect the T cells of a patient to kill the cancer cells. In this Review, we summarize the different approaches used by therapeutic antibodies to target cancer cells. We discuss their mechanisms of action, the structural basis for target specificity, clinical applications and the ongoing research to improve efficacy and reduce toxicity. #drugdiscovery #cancerresearch #immunooncology #immunotherapy #bites #tcells #adc #tcelltherapy #scientificresearch #sciencecommunication

Merck’s Phase 3 KEYNOTE-522 Trial: A Milestone in TNBC Treatment Merck recently announced that its Phase 3 KEYNOTE-522 trial successfully met its primary endpoint of overall survival (OS) in patients with high-risk early-stage Triple Negative Breast Cancer (TNBC). This is a significant breakthrough, as TNBC is an aggressive subtype of breast cancer that lacks the estrogen receptor (ER), progesterone receptor (PR), and HER2—common targets of many existing therapies. Due to these challenges, TNBC patients often face poor prognosis and limited treatment options. The KEYNOTE-522 trial tested the combination of pembrolizumab, a PD-1 inhibitor, and chemotherapy. This innovative treatment approach has the potential to improve survival outcomes for high-risk TNBC patients, highlighting the growing role of immunotherapy in addressing unmet needs in cancer treatment. MDA-MB-231: A Key Model for TNBC Research In my previous role as Director of Operations at Washington Biotechnology, I had the opportunity to collaborate on a study examining the MDA-MB-231 breast cancer model. Published in a peer-reviewed journal, this study demonstrated the broad anti-cancer activity induced by Targeted Nutrients Deprivation (TND)—a strategy that deprives cancer cells of non-essential amino acids critical for their survival. Unlike normal cells, cancer cells rely heavily on these amino acids, making them a promising target for cancer therapies (Li et al., 2022). This study also included data from other cancer models, such as head and neck cancer (Fadu, A253), pancreatic cancer (PANC-1), and prostate cancer (PC3). In addition, I had previously shared growth curve data from the BT474 model, a triple-positive breast cancer cell line, in another collaboration (Yang et al., 2023). At Noble Life Sciences Since joining Noble Life Sciences last year, I have had the privilege of collaborating with an exceptional team focused on advancing research in cancer therapeutics and autoimmune diseases. As a full-service contract research organization, we conduct both GLP and non-GLP studies, supporting everything from proof-of-concept research to preclinical safety and efficacy evaluations. For more information, visit www.noblelifesci.com. If you are interested in discussing cancer studies, autoimmune research, or custom models, please feel free to reach out. References: 1. Li, Z., Zhou, S., Yang, X., Li, X., Yang, G. X., Chant, J., ... & Wang, X. (2022). Broad anti-cancer activity produced by Targeted Nutrients Deprivation (TND) of multiple non-essential amino acids. Nutrition and Cancer, 74(7), 2607-2621. 2. Yang, Q., Chen, H., Ou, C., Zheng, Z., Zhang, X., Liu, Y., ... & Wang, L. X. (2023). Evaluation of Two Chemoenzymatic Glycan Remodeling Approaches to Generate Site-Specific Antibody–Drug Conjugates. Antibodies, 12(4), 71.