Preliminary clinical study of personalized neoantigen vaccine therapy for microsatellite stability (MSS)-advanced colorectal cancer

Cancer Immunol Immunother. 2023 Jul;72(7):2045-2056. doi: 10.1007/s00262-023-03386-7. Epub 2023 Feb 16.

Abstract

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS-CRC patients with postoperative recurrence or metastasis.

Keywords: Colorectal cancer; Immunotherapy; MSS; Neoantigen; Personalized vaccine.

Publication types

  • Clinical Trial

MeSH terms

  • Antigens, Neoplasm
  • Cancer Vaccines* / therapeutic use
  • Colorectal Neoplasms* / genetics
  • Humans
  • Immunotherapy / methods
  • Immunotherapy, Active
  • Microsatellite Repeats
  • Quality of Life

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines