Purpose: Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (α DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7.
Materials and methods: αDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed αDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay.
Results: The αDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the αDC1s were loaded with tumor antigens. The αDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by αDC1s loaded with apoptotic MCF-7 cells.
Conclusion: Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.
Keywords: Allogeneic; Breast neoplasms; Cytotoxic T lymphocytes; Dendritic cells; Immunotherapy.