4.3 Article

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

Journal

BIOCHEMISTRY AND CELL BIOLOGY
Volume 99, Issue 4, Pages 435-446

Publisher

CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/bcb-2020-0559

Keywords

peripheral blood mononuclear cells; dendritic cells; peptide vaccine; breast cancer; active immunity

Funding

  1. Mashhad University of Medical Sciences [961611]
  2. National Institute for Medical Research Development (NIMAD) [963611]

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The study compared the prophylactic effects of vaccines based on dendritic cells (DCs) and peripheral blood mononuclear cells (PBMCs) in a mouse model of breast cancer. It was found that the PBMC-based vaccine was more effective in enhancing protective immune responses, making it a simpler and more cost-effective candidate vaccine compared to DC-based vaccines.
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-gamma, granzyme B, and IL-10 were detected in T cells. Additionally, IFN-gamma 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-gamma(+), CD8(+) IFN-gamma(+), 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.

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