How to build a cancer vaccine, and whether they will work this time

5 hours ago

Cancer vaccines discussed are therapeutic, not preventive, and target existing cancer in patients.
Traditional Tumor-Associated Antigen (TAA) vaccines have largely failed due to immune tolerance and weak responses.
Neoantigens, arising from tumor mutations, are more promising as they are unique to cancer and avoid central tolerance.
Predicting which neoantigens are presented on MHC and immunogenic is complex, relying on sequencing, bioinformatics, and evolving models.
Recent successes (e.g., BioNTech's BNT122 in pancreatic cancer) show potential, but results vary by cancer type and setting.
Challenges include immunodominance, tumor heterogeneity, and the difficulty of immunopeptidomics for antigen validation.
Delivery platforms matter; mRNA vaccines can elicit T-cell responses better than older protein-based vaccines.
Checkpoint inhibitors enhance cancer vaccine efficacy by preventing T-cell suppression.
Shared neoantigen vaccines (e.g., targeting KRAS mutations) offer off-the-shelf potential but are limited by recurrence patterns.
The field shows renewed optimism due to advances in sequencing, mRNA delivery, and immunotherapy, but significant hurdles remain for widespread efficacy.

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