Intranodal Administration of Neoantigen Peptide-loaded Dendritic Cell Vaccine Elicits Epitope-specific T Cell Responses and Clinical Effects in a Patient with Chemorefractory Ovarian Cancer with Malignant Ascites

Immunol Invest. 2021 Jul;50(5):562-579. doi: 10.1080/08820139.2020.1778721. Epub 2020 Jul 13.

Abstract

Chemorefractory ovarian cancer has limited therapeutic options. Hence, new types of treatment including neoantigen-specific immunotherapy need to be investigated. Neoantigens represent promising targets for personalized cancer immunotherapy. We here describe the clinical and immunological effects of a neoantigen peptide-loaded DC-based immunotherapy in a patient with recurrent and chemoresistant ovarian cancer. A 71-year-old female patient with chemorefractory ovarian cancer and malignant ascites received intranodal vaccination of DCs loaded with four neoantigen peptides that were predicted by our immunogenomic pipeline. Following four rounds of vaccinations with this therapy, CA-125 levels were remarkably declined and tumor cells in the ascites were also decreased. Concordantly, the tumor-related symptoms such as respiratory discomfort improved without any adverse reactions. The reactivity against one HLA-A2402-restricted neoantigen peptide derived from a mutated PPM1 F protein was detected in lymphocytes from peripheral blood by IFN-γ ELISPOT assay. Furthermore, the neoantigen (PPM1 F mutant)-specific TCRs were detected in the tumor-infiltrating T lymphocytes post-vaccination. Our results showed that vaccination with intranodal injection of neoantigen peptide-loaded DCs may have clinical and immunological impacts on cancer treatment.

Keywords: Neoantigen; dendritic cell vaccine; epitope-specific T cell; intra-nodal administration; malignant ascites.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antigen Presentation
  • Antigens, Neoplasm / immunology
  • Ascites / immunology
  • Ascites / therapy*
  • CA-125 Antigen / blood
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology*
  • Drug Resistance, Neoplasm
  • Enzyme-Linked Immunospot Assay
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Immunotherapy / methods*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / therapy*
  • Peptides / immunology
  • Sentinel Lymph Node / immunology*
  • T-Lymphocytes / immunology*
  • Tumor Burden
  • Vaccination

Substances

  • Antigens, Neoplasm
  • CA-125 Antigen
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Peptides