Cell Therapy with Human Reprogrammed CD8+ T-Cells Has Antimetastatic Effects on Lewis Lung Carcinoma in C57BL/6 Mice.

Abstract

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.

• Authors: Evgenii G Skurikhin, Olga Pershina, Natalia Ermakova, Angelina Pakhomova, Mariia Zhukova, Edgar Pan, Lubov Sandrikina, Darius Widera, Lena Kogai, Nikolai Kushlinskii, Aslan Kubatiev, Sergey G Morozov, Alexander Dygai
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 24 (Dec 12 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36555420 (Publication Type: Journal Article)

Chemical References

• Programmed Cell Death 1 Receptor
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Mice
• Humans
• Carcinoma, Lewis Lung (therapy, pathology)
• Mice, Inbred C57BL
• CD8-Positive T-Lymphocytes (pathology)
• Follow-Up Studies
• Programmed Cell Death 1 Receptor
• Lung Neoplasms (therapy, secondary)
• Mitogen-Activated Protein Kinase Kinases