Immunosurgical resection of host tissues mediated by a novel dendritic cell-based vaccine proficient in the promulgation of TH1 immunity by exploitation of the p43/sCTLA-4 axis (P4248)

Abstract

Abstract The current understanding of TH1 polarization and the central role dendritic cells (DC) play in skewing such a response engender hope that DC-based vaccines may ultimately be capable of promoting therapeutic efficacy against recalcitrant pathogens and neoplastic self. However, to date the development of such a vaccine has been unsuccessful presumably because the full panoply of signals required for promulgation of bona fide TH1 immunity remains uncharacterized. Recently, our group demonstrated that synergistic loading of DC with homologous MHC class I and II antigens generates a powerful TH1 response significantly stronger and more specific than that generated by alternatively-loaded DC. Using this approach, we developed ‘TH1 DC’ vaccines against both autologous prostate and seminal vesicle (SV) in the wild type mouse. The data indicate that vaccines generated by homologous antigenic matching can overcome peripheral tolerance, producing a clinical result reminiscent of surgical resection. Translation of this platform to cancer immunotherapy has shown preliminary success against established tumors in inbred mouse models as well as spontaneous canine oligodendrocytomas. We demonstrate that these results are in part dependent upon the newly-characterized AIMp1(p43)/sCTLA-4 axis and comment upon the important role of this axis in the development of TH1 immunity as well as its applicability to cancer immunotherapy.