Cell Therapy with Human Reprogrammed CD8 + T-Cells Has Antimetastatic Effects on Lewis Lung Carcinoma in C57BL/6 Mice.
Evgenii G SkurikhinOlga Victorovna PershinaNatalia ErmakovaAngelina Vladimirovna PakhomovaMariia ZhukovaEdgar PanLubov SandrikinaDarius WideraLena KogaiNikolai KushlinskiiAslan KubatievSergey G MorozovAlexander DygaiPublished in: International journal of molecular sciences (2022)
Using a model of Lewis lung carcinoma (LLC) in vitro and in vivo, we previously demonstrated increased antitumor activity in CD8 + T-cells reprogrammed with an MEK inhibitor and PD-1 blocker. In this follow-up study, we carried out the reprogramming of human CD8 + T-cells (hrT-cell) using the MEK inhibitor and PD-1 blocker and targeted LLC cells. The effects of hrT-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 an 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.
Keyphrases
- cell therapy
- cancer therapy
- induced apoptosis
- endothelial cells
- cell cycle arrest
- stem cells
- mesenchymal stem cells
- mouse model
- pi k akt
- induced pluripotent stem cells
- drug delivery
- endoplasmic reticulum stress
- cancer stem cells
- pluripotent stem cells
- signaling pathway
- oxidative stress
- risk assessment
- high throughput
- immune response
- human health
- insulin resistance
- adipose tissue
- angiotensin ii
- dendritic cells
- high fat diet induced