126 IMCgp100: A novel bi-specific biologic for the treatment of malignant melanoma

Results: Systemic WT1-pTj treatment protected against metastatic melanoma in immune competent but not in immune deficient animals. Remarkably, peptide-activated syngeneic DCs ex vivo protected against metastatic melanoma, even in animals with established pulmonary nodules. By culturing CD11c+ cells isolated from cervical lymph nodes of WT1pTj-treated animals developing metastatic melanoma, we found that the peptide induced phenotypic maturation of DCs (e.g. upregulation of CD40, MHC-II and CD86) and enhanced production of type-1 cytokines, such as IL-6 and IL-12. Simultaneously, a marked decrease in TGF-b1 production was observed in DCs retrieved from WT1-pTj-treated mice. Moreover, the WT1-pTj-mediated antitumor activity was associated with significantly augmented frequency of tumor-infiltrating lymphocytes (CD8+ and CD4+) and NK1.1+ cells, and down-regulation of splenic CD4+ FoxP3+ regulatory T cells. Conclusions: The present results show the immunomodulatory role of WT1-pTj and indicate that the WT1-derived peptide may act as a potent adjuvant in cancer immunotherapy. Supported by FAPESP no. 2010/51423-0 and the Brazilian National Research Council (CNPq).