Development of Effective T-Lymphocyte-Based Immunotherapy Strategies
Cyctotoxic T Lymphocytes (CTL) play an essential role in the elimination of tumors. Our group has been studying the mechanisms that regulate the response of CTLs with the aim of developing effective strategies for the treatment of cancer. Tumors have developed a number of inhibitory mechanisms, known as immune checkpoints, that allow them to elude the CTLs. By using antibodies, it is easy to block inhibitory molecules present in the cell membranes (PD1, PDL-1, CTLA4). However, there are also intracellular immune checkpoints that could be regulated by means of genetic modification, but blocking these checkpoints is still a challenge.
Our current area of research is aimed at improving the efficacy of adoptive cellular transfer (ACT) of tumor-infiltrating T lymphocytes (TIL). ACT-TIL consists of treating patients with T lymphocytes isolated from their own tumors. The strategies we are developing are based on the following: (i) identification of biomarkers for the selection of tumor-specific TILs and (ii) blocking intracellular immune checkpoints through genetic modification of the TILs. In this regard, we are studying the effect of the regulation of key transcription factors for the activation/differentiation of CTLs on the antitumor efficacy of ACT-TIL.