Neoantigen
A protein fragment created by a tumour mutation that the immune system has never seen before, so it can attack it without harming normal cells.
Arise from missense mutations, frameshifts, fusions, and splice variants; must be processed and presented on the patient's HLA. Predicted computationally (binding affinity, expression, clonality). The targets of personalised mRNA vaccines and neoantigen-specific TCR-T; higher TMB means more candidates.
For the first time a randomised trial suggests that a vaccine tailored to an individual's tumour can reduce relapse when combined with immunotherapy, which is a proof of concept for a field that had failed for decades. Nothing changes for patients yet: the trial was small, the confidence interval crossed one, and the phase 3 trial in melanoma (and parallel trials in lung and other cancers) must confirm it. If it does, personalised mRNA vaccines could become a routine adjunct to checkpoint inhibitors after surgery.
Pancreatic cancer was thought to be immunologically inert because of its low mutation burden; this study showed that with the right vaccine platform its few neoantigens can still be targeted. It is the strongest human evidence so far that personalised cancer vaccines can generate durable, tumour-specific immunity, and it justifies the randomised trials now running in pancreatic cancer and melanoma. Benefit is not yet proven, because responders may simply have had more immunogenic tumours.
Because Lynch syndrome tumours make the same abnormal proteins in almost every patient, a single vaccine could in principle be given to carriers before cancer develops. This small trial showed the concept is safe and immunogenic; whether it prevents cancer requires the randomised trials now being planned.
This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.
Lung cancers keep evolving after they form, and it is ongoing chromosomal instability rather than the number of mutations that best predicts who will relapse. This gives a rationale for targeting the earliest (clonal) drivers and neoantigens and for tracking evolution in blood after surgery.
This small trial explained why colorectal cancer had seemed immune-resistant (most is MMR-proficient) and established the principle that a genomic feature, not the tissue of origin, can predict immunotherapy response. It led directly to the 2017 tissue-agnostic approval of pembrolizumab and to routine MMR/MSI testing of many cancers. Every patient with advanced dMMR cancer should now be considered for checkpoint blockade.
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not linked directly; found by shared links- CompanyBioNTech
Shares Vaccines aimed only at mutations shared by every tumour cell, University Cancer Center Mainz (UCT Mainz) / Universitätsmedizin Mainz, Personalised cancer vaccines at commodity cost through fully automated manufacturing, Personalised vaccines given only when the blood test turns positive.
- ProductAutogene cevumeran
Shares What makes a neoantigen actually immunogenic?, University Cancer Center Mainz (UCT Mainz) / Universitätsmedizin Mainz, Personalised cancer vaccines at commodity cost through fully automated manufacturing, Personalised vaccines given only when the blood test turns positive.
- TechnologyOff-the-shelf cancer vaccines
Shares Nina Bhardwaj, Nouscom, Vaccinate against the resistance mutation before it takes over, A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approval.
- TermTumour mutational burden (TMB)
Shares Timothy A. Chan, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery, Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer.
- CompanyModerna
Shares Vaccines aimed only at mutations shared by every tumour cell, Personalised cancer vaccines at commodity cost through fully automated manufacturing, Personalised vaccines given only when the blood test turns positive, KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery.
- TrialINTerpath-001 (V940-001)
Shares Vaccines aimed only at mutations shared by every tumour cell, KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery, Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer, Intismeran autogene.
- TermMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)
Shares Nouscom, A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approval, A randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancers, First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers.
- IdeaCancer interception vaccines for high-risk carriers
Shares A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approval, A randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancers, First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers.