Preventive cancer vaccination with P5 HER-2/neo-derived peptide‐pulsed peripheral blood mononuclear cells in a mouse model of breast cancer

Author:

Dehghan-Manshadi Mahdi12,Nikpoor Amin Reza3,Hadinedoushan Hossein2,Zare Fateme2,Sankian Mojtaba4,Fesahat Farzaneh2,Tahoori Mohammad Taher2,Jaafari Mahmoud Reza5,Rafatpanah Houshang6

Affiliation:

1. Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

2. Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

3. Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

4. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

5. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

6. Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

This study compared the prophylactic effects from vaccines based on dendritic cells (DCs) and peripheral blood mononuclear cells (PBMCs) by pulsing the cells in-vitro with p5 peptide. The different test groups of mice were injected with free peptide or with peptide pulsed with DCs or PBMCs. Two weeks after the last booster dose, immunological tests were performed on splenocyte suspensions from three mice in each group and the remaining mice (5/each group) were evaluated for tumor growth and survival time. The levels of IFN-γ, granzyme B, and IL-10 were detected in T cells. Additionally, IFN-γ and perforin as well as mRNA levels of some genes associated with immune responses were assessed after challenging the splenocytes with TUBO cells. A significant increase was observed in frequency of CD4+ IFN-γ+, CD8+ IFN-γ+, and CD8+ granzyme B+ T cells, and the perforin of supernatants from mice in the DC and PBMC treatment groups. Significant expression levels of Fas ligand (FasL) and forkhead box P3 (Foxp3) were observed in the DC and PBMC groups. These responses led to smaller tumors and longer survival time in our mouse model of breast cancer. The efficacy of the PBMC-based vaccine in improving the protective immune response makes it a simpler and less expensive candidate vaccine compared with DC-based vaccines.

Publisher

Canadian Science Publishing

Subject

Cell Biology,Molecular Biology,Biochemistry

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