Effect of Adoptive T cell Therapy on VEGF Signaling Pathway in DMH-Induced Colon Cancer in Balb/c Mice (Lebanon)
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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The Past Head, General Administration of Pharmaceutical Care at Ministry of Health,
Saudi Arabia Critical Care/TPN
Clinical Pharmacist Ministry of Health,
Riyadh, Saudi Arabia.
Department of Radiation Oncology
Asahi University Hospital
Gifu city, Gifu, Japan
Maher Abdel Fattah Al-Shayeb
Department of Surgical Sciences, Ajman University, UAE
Institute of Gynecology and Obstetrics, Medical University of Lodz, I Clinic of Gynecology and Gynecological Oncology (Lodz, Poland)
Head of the Oncology Gynecology Clinic, Oncology Center - Instytut im. Maria Sklodowska Curie, Department in Krakow (Krakow, Poland)