Induction of protective cytotoxic T cell responses by a B cell-based cellular vaccine requires stable expression of antigen

B cell-based cellular vaccines represent a promising approach to active immunotherapy of cancer complementing the use of dendritic cells, especially in pediatric patients and patients with low bone marrow reserves. B cells can be easily prepared in large numbers and readily home to secondary lymphoid organs, the primary site of induction of cytotoxic T lymphocyte (CTL) responses. However, most B cell-based vaccines tested so far failed to induce functional and protective CTLs in in vivo models. Here we demonstrate that B cells activated via the Toll like receptor-9 (TLR-9) and CD40 up-regulate surface expression of MHC and costimulatory molecules, produce IL-12, and exhibit potent antigen-presenting properties in vitro. Importantly, while administration of peptide-coated or transiently transfected B cells fails to induce immune responses, therapeutic immunization with low numbers of genetically modified B cells stably expressing antigen results in an induction of functional CTLs and protection against the growth of tumor in an animal model. Following activation, B cells partially loose their ability to home to organized lymphoid tissue due to the shedding of CD62L; however, this property can be restored by expression of protease-resistant mutant of CD62L. In summary, the data presented in this report suggest that genetically modified activated B cells represent a promising candidate for a cancer vaccine eliciting functional systemic CTLs.