Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer.
Nature
; 547(7662): 222-226, 2017 07 13.
Article
in En
| MEDLINE
| ID: mdl-28678784
ABSTRACT
T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. 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 ß2-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. Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA
/
Cancer Vaccines
/
Precision Medicine
/
Melanoma
/
Mutation
Limits:
Humans
Language:
En
Journal:
Nature
Year:
2017
Document type:
Article
Affiliation country: