Genomic instability of ovarian cancer (OvCa) cells and the resulting frequent loss or reduction of HLA expression and function facilitate immune avoidance of this aggressive cancer. The goal of this Project is to develop an effective mode of immunotherapy capable of targeting both MHC-positive and MHC-negative variants of OvCa and counteracting local immune suppression, known to contribute to poor prognosis in OvCa patients. We observed that type-1-polarized DCs (?DC1s), a novel type of DCs developed by our group, effectively cross-present OvCa-related antigens and induce high numbers of MHC class l-restricted CTLs capable of recognizing defined OvCa-related antigenic epitopes. However aDC1-induced CTLs also express elevated levels of NK receptors, NKG2D- and DNAM1. Such
We plan to develop a new immunotherapy of ovarian cancer, combining a new highly-potent autologous dendritic cells vaccine (?DC1s) with the local infusion of ex-vivo ?DC1-induced effector CD8+ T cells (CTLs) able of recognizing tumor cells both in a classical (TCR-dependent) and TCR-independent manner. We anticipate that such treatment will promote destruction of residual tumor cells in patients with advanced ovarian cancer treated with chemotherapy, independently on their ability to mutate and evade classical forms of immune recognition, preventing or delaying tumor recurrence.
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