Wnt/β-cateninová a mTOR signalizace v regulaci fenotypu a cytotoxické aktivity T buněk pro adoptivní buněčnou imunoterapii nádorových onemocnění

Stakheev, Dmitry

1. Abstract (EN) The adoptive cellular immunotherapy (ACI) based on ex vivo produced T cells is a modern treatment modality of cancer. However, the ex vivo production of T cells with high therapeutic efficacy is far to be well established. Wnt/β-catenin and mTOR signaling have been shown to affect both cancer cells and immune cells. Therefore, the modulation of these pathways seems to be perspective for the production of T cells with superior therapeutic efficacy. The aim of our project was to investigate, how interventions into Wnt/β-catenin and mTOR signaling during the ex vivo production of tumor-associated antigen-specific T cells could improve the production of T cells with a desired and controlled phenotype that would best fit for use in ACI of cancer. In the first part of our study, we investigated the role of Wnt/β-catenin inhibition by XAV939 on cancer cell elimination by lymphocytes from patients with localized biochemically recurrent prostate cancer (BRPCa). We found that preconditioning BRPCa lymphocytes with 5 µM XAV939 accelerated the elimination of LNCaP and PC3 cells during the coculturing. However, during subsequent re-coculturing with fresh LNCaP cells, BRPCa lymphocytes were no longer able to eliminate cancer cells unless coculturing and re-coculturing were performed in the presence of...

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