Seonglae ChoLimitation
Cancer vaccine development is challenging because cancer-derived neoantigens are difficult to distinguish from normal proteins, making immune response induction difficult, and there is no comparison or benchmarking between modalities (mRNA, peptide, DNA, etc.). The core problem is that the process of accurately predicting and presenting neoantigens and verifying their interaction with T-cell receptors (TCRs) is extremely complex, with prediction algorithms having immunogenicity hit rates of less than 5%.
Conclusion
Tumor heterogeneity and preclinical indicators alone make it difficult to guarantee actual tumor removal effects, making surface expression verification (immunopeptotyping) and functional screening (single-cell TCR sequencing, etc.) essential. Future challenges include reducing the cost of personalized mRNA manufacturing (approximately $150,000) and manufacturing complexity through microfluidics and cell-free synthesis technologies, as well as developing preventive vaccines targeting broad common antigens.
The Failures and Futures of Cancer Vaccines
The cancer vaccine field has yet to become a systematic science despite decades of work and a steadily rising number of clinical trials since the first clinical PoC a decade ago. A core problem facing cancer vaccine development lies in the nature of neoantigens themselves. In infectious diseases, the antigenic
https://www.mackenziemorehead.com/the-failures-and-futures-of-cancer-vaccines/
introduction to cancer vaccines
cancer neoantigens
For cells to become cancerous, they must have mutations that cause
uncontrolled replication and mutations that prevent that uncontrolled
replication from causing apoptosis. Because cancer requires several
mutations, it often begins with damage to mutation-preventing mechanisms. As
such, cancers often have many mutations not required for their growth, which
often cause changes to structure of some surface proteins.The
modified surface proteins of cancer cells are called "neoantigens". An
approach to cancer treatment that's currently being researched is to
identify some specific neoantigens of a patient's cancer, and create a
personalized vaccine to cause their immune system to recognize them. Such
vaccines would use either mRNA or synthetic long peptides. The steps
required are as follows:
https://www.bhauth.com/blog/biology/cancer%20vaccines.html