Cell therapy with human reprogrammed CD8+ T-cells has antimetastatic effects on Lewis Lung Carcinoma in C57BL/6 mice

Skurikhin, E. G., Pershina, O., Ermakova, N., Pakhomova, A., Zhukova, M., Pan, E., Sandrikina, L., Widera, D. ORCID: https://orcid.org/0000-0003-1686-130X, Kogai, L., Kushlinskii, N., Kubatiev, A., Morozov, S. and Dygai, A. (2022) Cell therapy with human reprogrammed CD8+ T-cells has antimetastatic effects on Lewis Lung Carcinoma in C57BL/6 mice. International Journal of Molecular Sciences, 23 (24). 15780. ISSN 1661-6596 doi: 10.3390/ijms232415780

Abstract/Summary

Using a model of Lewis lung carcinoma (LLC) in vitro and in vivo, we have previously demonstrated an increased antitumor activity of CD8+ T-cells reprogrammed with MEK inhibitor and PD-1 blocker. In this follow-up study, we carried out reprogramming of human CD8+ T-cells (hrT-cell) using MEK inhibitor and PD-1 blocker and targeted LLC cells. The effects of hrT-cells cell therapy were studied in a mouse model of spontaneous metastasis of a solid LLC tumor. We found antimetastatic activity of hrT-cells, a decrease in the number of cancer cells and cancer stem cells in the lungs, and an increase in the number of T-cells in the blood (including effector T-cells). Thus, reprogramming of human CD8+ T-cells with MEK inhibitor and PD-1 blocker with targeted training by tumor target cells is a potential platform for developing a new approach to targeted lung cancer therapy.