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

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.

Overexpression of Apolipoprotein C1 (APOC1) in Clear Cell Renal Cell Carcinoma and Its Prognostic Significance

“…These genes co-expressed with APOC1 were mainly expressed in dendritic cells, B cells, and CD4 cells. Dendritic cells are the most important antigen-presenting cells, which can present antigens via both MHC-I and MHC-II [ 27 ], and play a primary role in antigen presentation to CD4 cells. Dendritic cells can determine cancer immune responses by regulating immune activation and tolerance [ 28 ], as well as leading to the development of autoantibody through B cells [ 29 ].…”

Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy

“…Murine BM progenitor cells were used for DCs preparation according to the previously described method 19 , 39 and characterized for maturation state. 5 × 10 5 matured DCs (by LPS) (Fig.…”

Dendritic Cell Tumor Vaccination via Fc Gamma Receptor Targeting: Lessons Learned from Pre-Clinical and Translational Studies

“…Taken together, IgG:Ag ICs provide an attractive entry route for therapeutic anticancer DC vaccination protocols with clear advantages over vaccinations with “naked” Ag. Importantly, the use of the whole Ag protein over human leukocyte antigen (HLA)-restricted peptide-based [ 98 ] tumor vaccination protocols could also mean more patients would be eligible for such treatments.…”

“…Taken together, IgG:Ag ICs provide an attractive entry route for therapeutic anticancer DC vaccination protocols with clear advantages over vaccinations with "naked" Ag. Importantly, the use of the whole Ag protein over human leukocyte antigen (HLA)-restricted peptide-based [98] tumor vaccination protocols could also mean more patients would be eligible for such treatments. Haptens are small molecules engineered in such a way that, in combination with a larger carrier such as a protein [99][100][101], they can elicit the production of antibodies that bind specifically to it.…”