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Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients
- Source :
- Cancer Immunology, Immunotherapy. 69:1375-1387
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4+ and/or CD8+ T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4+ and CD8+ T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.Trial registration ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).
- Subjects :
- CD4-Positive T-Lymphocytes
Male
Cancer Research
Lung Neoplasms
Imiquimod
CD8-Positive T-Lymphocytes
0302 clinical medicine
Carcinoma, Non-Small-Cell Lung
Immunology and Allergy
Precision Medicine
biology
Middle Aged
Prognosis
Gene Expression Regulation, Neoplastic
Survival Rate
medicine.anatomical_structure
Oncology
Female
Antibody
medicine.drug
Adult
Adolescent
Cyclophosphamide
T cell
Immunology
Cancer Vaccines
complex mixtures
03 medical and health sciences
Antigen
Antigens, Neoplasm
parasitic diseases
Biomarkers, Tumor
medicine
Humans
Lung cancer
Aged
business.industry
Gene Expression Profiling
Dendritic Cells
Dendritic cell
medicine.disease
digestive system diseases
Cancer research
biology.protein
Immunization
Glioblastoma
business
CD8
Follow-Up Studies
030215 immunology
Subjects
Details
- ISSN :
- 14320851 and 03407004
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Cancer Immunology, Immunotherapy
- Accession number :
- edsair.doi.dedup.....3005d50db631afc98b48e76193e17e0a