期刊
VACCINE
卷 38, 期 35, 页码 5665-5677出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2020.06.055
关键词
Melanoma; DC-based vaccine; Liposome; Gp100; PD-1 monoclonal antibody
资金
- Kashan University of Medical Sciences [9523]
- Mashhad University of Medical Science [941426]
Background: Targeting antigens to dendritic cells (DCs) via nanoparticles is a powerful strategy which improves the efficacy of ex vivo antigen-pulsed DC vaccines. Methods: In this study, liposomes were first decorated with gp100(25-33) self-antigen and then characterized. Then, DCs were pulsed ex vivo with liposomal gp100 and injected subcutaneously in mice bearing B16F10 established melanoma tumors in combination with anti-PD-1 therapy. Results: Treatment with liposomal pulsed DC vaccine elicited the strongest anticancer immunity and enhanced intratumoral immune responses based on infiltration of gp100-specific CD4+ and CD8+ T cells to the tumor leading to significant tumor growth regression and prolonged survival rate. Treatment with liposomal pulsed DC vaccine also markedly enhanced specific cytotoxic T lymphocytes (CTL) responses with a significant higher titer of IFN-gamma in the spleen. Moreover, a significant increase of PD-1 expressing CD8+ tumor infiltrating lymphocytes (TILs) was detected in tumors. Conclusion: Our results demonstrate an optimum dose of liposomal gp100 significantly increases the efficacy of anti-PD-1 therapy in mice and might be an effective strategy to overcome resistance to anti-PD-1 therapy. (C) 2020 Elsevier Ltd. All rights reserved.
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