T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient.
Recently the concept of individualized mutanome vaccines was introduced and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations.
Researchers have reported the first-in-human application of this concept in melanoma.
A process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient was set up.
All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit percentages.
Vaccine-induced T cell infiltration and neo-epitope-specific killing of autologous tumour cells were shown in post-vaccination resected metastases from two patients.
The cumulative rate of metastatic events was highly significantly reduced after the start of vaccination, resulting in a sustained progression-free survival.
Two of the five patients with metastatic disease experienced vaccine-related objective responses.
One of these patients had a late relapse owing to outgrowth of beta2-microglobulin-deficient melanoma cells as an acquired resistance mechanism.
A third patient developed a complete response to vaccination in combination with PD-1 blockade therapy.
The study has demonstrated that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer. ( Xagena )
Sahin U et al, Nature 2017 doi:10.1038/nature23003