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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.
- Source :
-
Immunological investigations [Immunol Invest] 2021 Jul; Vol. 50 (5), pp. 562-579. Date of Electronic Publication: 2020 Jul 13. - Publication Year :
- 2021
-
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.
- Subjects :
- Aged
Antigen Presentation
Antigens, Neoplasm immunology
Ascites immunology
CA-125 Antigen blood
Drug Resistance, Neoplasm
Enzyme-Linked Immunospot Assay
Epitopes, T-Lymphocyte immunology
Female
Humans
Ovarian Neoplasms immunology
Peptides immunology
Tumor Burden
Vaccination
Ascites therapy
Cancer Vaccines immunology
Dendritic Cells immunology
Immunotherapy methods
Lymphocytes, Tumor-Infiltrating immunology
Ovarian Neoplasms therapy
Sentinel Lymph Node immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-4311
- Volume :
- 50
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Immunological investigations
- Publication Type :
- Academic Journal
- Accession number :
- 32660279
- Full Text :
- https://doi.org/10.1080/08820139.2020.1778721