Enhanced immune response induced by P5 HER2/neu-derived peptide-pulsed dendritic cells as a preventive cancer vaccine

Gholizadeh, Z. and Tavakkol-Afshari, J. and Nikpoor, A. R. and Jalali, S. A. and Jaafari, M. R. (2018) Enhanced immune response induced by P5 HER2/neu-derived peptide-pulsed dendritic cells as a preventive cancer vaccine. Journal of Cellular and Molecular Medicine, 22 (1). pp. 558-567.

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Abstract

Dendritic cells are special and powerful antigen-presenting cells that can induce primary immune responses against tumour-associated antigens. They can present antigens via both MHC-I and MHC-II, so they have the ability to stimulate both cytotoxic T lymphocytes and T helper cells. Furthermore, CD8+ cytotoxic T lymphocytes require activation by CD4+ T cells. This requires a CD4+T cell activator molecule, of which PADRE is one of the best. We chose an approach to use both of these important arms of the immune system. We prepared dendritic cells from mouse bone marrow, loaded them with our target peptides (P5 peptide alone or P5 + PADRE), and then injected these pulsed dendritic cells alone or in combination with CpG-ODN (as adjuvant) into BALB/C mice. After the last boosting dose, mice were inoculated with TUBO cells, which overexpress HER2/neu. Two weeks after the tumour cell injection, immunological tests were performed on splenocyte suspensions, and the remaining mice were evaluated for tumour growth and survival. Our data indicate the formulation that contains PADRE plus P5 loaded onto DC in combination with CpG-ODN was the most effective formulation at inducing immune responses. Interferon production in CD4+ and CD8+ gated cells, cytotoxicity rates of target cells and mice survival were all significantly greater in this group than in controls, and all the mice in this group were tumour-free throughout the experiment. Based on our results and the role of HER2/neu as a candidate in human immunotherapy, this approach may be an effective cancer treatment. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Item Type: Article
Additional Information: Cited By :3 Export Date: 16 February 2020 Correspondence Address: Jalali, S.A.; Department of Immunology, Medical School, Shahid Beheshti University of Medical SciencesIran; email: jalalia@sbmu.ac.ir
Uncontrolled Keywords: cancer dendritic Cells pan HLA-DR epitope peptide peptide vaccine cancer vaccine CpG oligodeoxynucleotide dendritic cell vaccine epidermal growth factor receptor 2 epitope gamma interferon HLA DR antigen interleukin 4 cytokine leukocyte antigen ovalbumin peptide animal cell animal experiment Article bone marrow derived dendritic cell cancer immunization CD4+ T lymphocyte CD8+ T lymphocyte controlled study cytotoxicity enzyme linked immunospot assay female flow cytometry gene overexpression immune response in vitro study in vivo study interferon production malignant neoplasm mouse nonhuman phenotype priority journal spleen cell survival tumor volume uptake assay animal Bagg albino mouse cell line cell survival dendritic cell fluorescence immunity immunology immunotherapy intracellular space metabolism neoplasm pathology tumor cell line Animals Antigens, CD Cancer Vaccines Cell Line, Tumor Cytokines Cytotoxicity, Immunologic Mice, Inbred BALB C Neoplasms Peptides Tumor Burden
Subjects: QW Microbiology and Immunology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 20 May 2020 04:51
Last Modified: 20 May 2020 04:51
URI: http://eprints.mums.ac.ir/id/eprint/17300

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