Effect of Adoptive T cell Therapy on VEGF Signaling Pathway in DMH-Induced Colon Cancer in Balb/c Mice (Lebanon)

Abstract

Author(s): Bou Hamdan M, Massaad M, Usta J, Jamilah Borjac

Colon cancer is the fourth most leading causes of cancer-related deaths worldwide accounting for nearly 7-10% of all cancers. Adoptive T Cell Therapy (ACT), a type of immunotherapy, was first developed using Tumor-Infiltrating Lymphocytes (TILs) whereby TILs from the cancer patients are isolated, expanded in vitro using a high concentration of Interleukin-2 (IL-2), and then injected back into the same patients. It was shown that chemotherapy-induced lymphodepletion prior to ACT activates the persistence and anticancer effectiveness of the injected cells. In this study, we aimed to determine the effect of Adoptive T cell therapy (CD8 T cell therapy) alone or in adjunct to Sorafenib on the Vascular Endothelial Growth Factor (VEGF) signaling pathway. CRC was induced in Balb/c mice using dimethylhydrazine injections once per week for 12 consecutive weeks. The mice were treated with either sorafenib, Adoptive T cell therapy or both. Colons were used for histological and molecular analysis. Gene expression was performed using RT-PCR. Sorafenib and/ or Adoptive T cell therapy aided in restoring the normal histology and structure of colon cancer tissue. Sorafenib and/or CD8 T cell treatment led to a decrease in the expression levels of VEGF-A, VEGFR-1, VEGFR-2, BRAF, mTOR, PI3K, KRAS and AKT as compared to untreated control Balb/c mice group. In conclusion, our findings may open up future work on the effect CD8 T cell therapy in colon cancer and on producing new anti-colon cancer therapeutic agents targeting these pathways. This study may be utilized as a base for immunotherapeutic research in colon cancer.

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