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.