{"entity":{"id":"idea-bio1-clonal-neoantigen-vaccines","kind":"idea","name":"Vaccines aimed only at mutations shared by every tumour cell","aka":[],"tldr":"Personal cancer vaccines target a list of mutations, some present in only part of the tumour, so the tumour can escape by losing them. Restricting vaccines and T-cell products to clonal mutations shared by every tumour cell, identified by multi-region sequencing, should close that escape route.","summary":"Clonal (truncal) neoantigens are present in all tumour cells, so an immune response to them cannot be escaped by subclonal antigen loss. Multi-region sequencing or high-purity clonality inference can identify them. Personalised mRNA vaccines and clonal-neoantigen-reactive T-cell products (such as those pioneered from TRACERx data) could be restricted to clonal targets and compared with unselected designs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["neoantigen-mrna-vaccine","til-therapy"],"targets":[],"drugs":[],"companies":["moderna","biontech"],"institutions":[],"pathways":[],"terms":["neoantigen"],"trials":["interpath-001"],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-immunotherapy-response"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccines or T-cell products restricted to clonal neoantigens produce fewer antigen-loss relapses and longer disease-free survival than products built from unselected neoantigen lists of equal size.","rationale":"Clonal neoantigen burden, not total burden, predicted checkpoint inhibitor response in lung and melanoma cohorts; escape by loss of subclonal antigens is a documented failure mode.","test":"Randomised phase 2 in the adjuvant setting comparing clonal-restricted versus standard neoantigen selection with the same vaccine platform; endpoint recurrence-free survival and antigen-loss at relapse.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":5},"route":"/ideas/idea-bio1-clonal-neoantigen-vaccines/","neighbours":{"technology":[{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"},{"id":"til-therapy","kind":"technology","name":"TIL therapy","route":"/technologies/til-therapy/"}],"company":[{"id":"biontech","kind":"company","name":"BioNTech","route":"/companies/biontech/"},{"id":"moderna","kind":"company","name":"Moderna","route":"/companies/moderna/"}],"term":[{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"}],"trial":[{"id":"interpath-001","kind":"trial","name":"INTerpath-001 (V940-001)","route":"/trials/interpath-001/"}],"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"paper":[{"id":"paper-tracerx-100-nejm-2017","kind":"paper","name":"TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse","route":"/key-papers/paper-tracerx-100-nejm-2017/"}]}}