Effects of An Anti-CTLA-4 Antibody Therapy on Metastatic Melanoma

Heidi Reichert, Qing Wang

Abstract


CTLA-4 is a co-inhibitory molecule that functions to inhibit T cell functions, essentially acting as a break on the immune system. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including anti-tumor immunity. These antibodies likewise trigger an expansion of tumor infiltrating Th1-like CD4 T cells. CTLA-4 blockade has demonstrated benefits in overall survival and harm reduction in the treatment of metastatic melanoma, which accounts for 80% of the 66,000 annual skin cancer deaths. More recently, efforts to combine anti-CTLA-4 antibodies with other forms of cancer treatment like radiotherapy and chemotherapy have proven to be successful. This study has focused on the modeling and analysis of the effects of anti-CTLA-4 antibody therapy alone on tumor growth using impulsive differential equations. The Jacobian matrix was constructed, evaluated at a tumor-free equilibrium, and evaluated for stability using experimental data. This project is supported by the NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence. 


Keywords


Tumor model; simulation

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