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Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma
- Source :
- Journal for Immunotherapy of Cancer, Journal for immunotherapy of cancer, vol 7, iss 1, Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-15 (2019)
- Publication Year :
- 2019
- Publisher :
- BioMed Central, 2019.
-
Abstract
- Background Cancer vaccines are designed to promote systemic antitumor immunity and tumor eradication. Cancer vaccination may be more efficacious in combination with additional interventions that may build on or amplify their effects. Methods Based on our previous clinical and in vitro studies, we designed an antigen-engineered DC vaccine trial to promote a polyclonal CD8+ and CD4+ T cell response against three shared melanoma antigens. The 35 vaccine recipients were then randomized to receive one month of high-dose IFNα or observation. Results The resulting clinical outcomes were 2 partial responses, 8 stable disease and 14 progressive disease among patients with measurable disease using RECIST 1.1, and, of 11 surgically treated patients with no evidence of disease (NED), 4 remain NED at a median follow-up of 3 years. The majority of vaccinated patients showed an increase in vaccine antigen-specific CD8+ and CD4+ T cell responses. The addition of IFNα did not appear to improve immune or clinical responses in this trial. Examination of the DC vaccine profiles showed that IL-12p70 secretion did not correlate with immune or clinical responses. In depth immune biomarker studies support the importance of circulating Treg and MDSC for development of antigen-specific T cell responses, and of circulating CD8+ and CD4+ T cell subsets in clinical responses. Conclusions DC vaccines are a safe and reliable platform for promoting antitumor immunity. This combination with one month of high dose IFNα did not improve outcomes. Immune biomarker analysis in the blood identified several predictive and prognostic biomarkers for further analysis, including MDSC. Trial registration NCT01622933. Electronic supplementary material The online version of this article (10.1186/s40425-019-0552-x) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
CD4-Positive T-Lymphocytes
Male
and promotion of well-being
Cancer Research
Skin Neoplasms
CD8-Positive T-Lymphocytes
Protein Engineering
0302 clinical medicine
Immunogenicity, Vaccine
Tumor immunity
80 and over
Cancer vaccine
Immunology and Allergy
Medicine
Melanoma
Cancer
Aged, 80 and over
Vaccines
Vaccines, Synthetic
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Immunogenicity
Combined Modality Therapy
Progression-Free Survival
3. Good health
Vaccination
medicine.anatomical_structure
3.4 Vaccines
Oncology
030220 oncology & carcinogenesis
HIV/AIDS
Molecular Medicine
Biomarker (medicine)
Female
Drug
Biotechnology
Research Article
Adult
T cell
Clinical Trials and Supportive Activities
Immunology
Shared antigens
lcsh:RC254-282
Cancer Vaccines
Dose-Response Relationship
Vaccine Related
03 medical and health sciences
Immune system
Antigen
Clinical Research
Antigens, Neoplasm
Humans
Antigens
Response Evaluation Criteria in Solid Tumors
Aged
Pharmacology
Dose-Response Relationship, Drug
business.industry
Prevention
Inflammatory and immune system
Synthetic
Interferon-alpha
Dendritic Cells
Prevention of disease and conditions
medicine.disease
Immune biomarkers
Good Health and Well Being
030104 developmental biology
Neoplasm
Immunization
business
Vaccine
CD8
Follow-Up Studies
Subjects
Details
- Language :
- English
- ISSN :
- 20511426
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal for Immunotherapy of Cancer
- Accession number :
- edsair.doi.dedup.....cf36d5e764b19a3d28371c3912141fad