Neoantigen Vaccines: Personalized Immunotherapy, Day 64

𝘕𝘦𝘰𝘢𝘯𝘵𝘪𝘨𝘦𝘯 𝘷𝘢𝘤𝘤𝘪𝘯𝘦𝘴 represent a cutting-edge approach in personalized immunotherapy, taking patient’s own immune system to specifically target 𝘵𝘶𝘮𝘰𝘳-𝘴𝘱𝘦𝘤𝘪𝘧𝘪𝘤 𝘮𝘶𝘵𝘢𝘵𝘪𝘰𝘯𝘴. Unlike classic vaccines, neoantigen vaccines are designed based on the unique mutational landscape of an individual’s tumor, relying on next-generation sequencing (NGS) and bioinformatic prediction to identify immunogenic epitopes [1,2]. 

𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺 𝗼𝗳 𝗔𝗰𝘁𝗶𝗼𝗻: 
Often delivered as 𝘮𝘙𝘕𝘈, 𝘱𝘦𝘱𝘵𝘪𝘥𝘦, or 𝘥𝘦𝘯𝘥𝘳𝘪𝘵𝘪𝘤 𝘤𝘦𝘭𝘭-𝘣𝘢𝘴𝘦𝘥 𝘧𝘰𝘳𝘮𝘶𝘭𝘢𝘵𝘪𝘰𝘯𝘴. Once administered, neoantigen epitopes are presented via MHC molecules to CD8+ and CD4+ T cells, priming cell response against tumor cells carrying these mutations [3]. This strategy minimizes off-target toxicity because the epitopes are not expressed in healthy tissues. 

𝗚𝗲𝗿𝗺𝗮𝗻 𝗥𝗲𝘀𝗲𝗮𝗿𝗰𝗵 𝗛𝗶𝗴𝗵𝗹𝗶𝗴𝗵𝘁𝘀: 
• Prof. Ugur Sahin’s group at BioNTech pioneered mRNA-based personalized cancer vaccines. [4]  
• Prof. Stefaan W. van Gool at the IOZK in Cologne uses patient-derived DCs loaded with tumor-specific antigens, including neoantigens, sometimes combined with oncolytic viruses, to prime adaptive T-cell responses against cancer [5] 

𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗣𝗼𝘁𝗲𝗻𝘁𝗶𝗮𝗹 𝗮𝗻𝗱 𝗖𝗵𝗮𝗹𝗹𝗲𝗻𝗴𝗲𝘀: 
Neoantigen vaccines are showing promise in melanoma, lung cancer, and colorectal cancer, especially when combined with checkpoint inhibitors. Current challenges include the variability in patient immune competence, tumor heterogeneity, and the rapid manufacturing required for a personalized approach. 

𝗦𝗽𝗲𝗰𝘂𝗹𝗮𝘁𝗶𝘃𝗲 𝗛𝘆𝗽𝗼𝘁𝗵𝗲𝘀𝗶𝘀: 
Could combining neoantigen vaccines with CAR-T or NK-CAR therapies enhance anti-tumor efficacy? One could envision a ´prime-and-boost´ approach where the vaccine primes endogenous T cells while engineered cells provide immediate cytotoxic activity. AI-driven approach and optimization fo existing CAR-T might snergistically envision. 

𝗤𝘂𝗲𝘀𝘁𝗶𝗼𝗻 𝗳𝗼𝗿 𝘁𝗵𝗲 𝗔𝘂𝗱𝗶𝗲𝗻𝗰𝗲: What do you think are the key bottlenecks preventing widespread clinical adoption of neoantigen vaccines? 

Stay tuned for 𝗗𝗮𝘆 𝟲𝟱: 𝗔𝗻𝘁𝗶𝗴𝗲𝗻 𝗘𝘀𝗰𝗮𝗽𝗲 & 𝗧𝘂𝗺𝗼𝗿 𝗛𝗲𝘁𝗲𝗿𝗼𝗴𝗲𝗻𝗲𝗶𝘁𝘆 

𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀: 
1. DOI: 10.1038/nature23003 
2. DOI: 10.1038/nature22991 
3. DOI: 10.1126/science.aaa4971 
4. https://www.biopharmadive.com/news/biontech-mrna-cancer-vaccine-pancreatic-cancer-roche/649865/ 
5. doi: 10.21037/tcr-23-603 

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