Vaccination with dendritic cells pulsed ex vivo with gp100 peptide-decorated liposomes enhances the efficacy of anti PD-1 therapy in a mouse model of melanoma.

Abstract

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 gp10025-33 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-γ 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.

• Authors: Mona Yazdani, Zahra Gholizadeh, Amin Reza Nikpoor, Mahdi Hatamipour, Behrang Alani, Hossein Nikzad, Nema Mohamadian Roshan, Javad Verdi, Mahmoud Reza Jaafari, Mahdi Noureddini, Ali Badiee
• Journal: Vaccine (Vaccine) Vol. 38 Issue 35 Pg. 5665-5677 (07 31 2020) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 32653275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Cancer Vaccines
• Liposomes
• Membrane Glycoproteins
• Neoplasm Proteins
• Peptides
• gp100 Melanoma Antigen

Topics

• Animals
• Cancer Vaccines
• Dendritic Cells
• Liposomes
• Melanoma (therapy)
• Membrane Glycoproteins
• Mice
• Neoplasm Proteins
• Peptides
• T-Lymphocytes, Cytotoxic
• Vaccination
• gp100 Melanoma Antigen