Optimization of PLGA microspheres for immunotherapy of tumors in the mouse model

The delivery of immune stimulating agents and antigens is a major requirement for successful immunotherapy of cancer. So far incomplete Freund’s adjuvant (IFA) was considered to be the “gold-standard” and is used in mice and humans. In this study we compared a mixture of IFA and the model antigen ovalbumin as well as the adjuvants CpG-oligodeoxynucleotides (CpG-ODN) and polyI:C to poly(lactideco-glycolide) (PLGA) microspheres (MS), which contain the antigen and the adjuvant. This study elucidates the potential of PLGA-MS to elicit substantial humoral and cellular immune responses after a single administration. A subsequent injection of recombinant vaccinia virus expressing ovalbumin increases the CTL response significantly. Furthermore, we could show that both, IFA and PLGA-MS, form a depot that accounts for a long-lasting potential to stimulate proliferation of CD4 and CD8 T cells, as well as in vivo cytotoxicity for at least 3 weeks after the immunization. In several tumor models we could show that PLGA-MS are at least equally efficient than IFA, if not better. In detail, PLGAMS show a potent protective potential and superior therapeutic efficacy compared to IFA.