Lymphocytes Genetically Engineered to Express Anti-MAGE-A3 Antigens Provoke Anti-Propagating Immune Responses in Malignant Melanoma Patients

Sarah Elizabeth Algino

Abstract


Current forms of treatment for melanoma such as chemotherapy, radiation, and the use of therapeutic agents such as IL-2 or vemurafenib are ineffective and highly toxic to melanoma patients. Increasing interest toward the field of immunotherapy has allowed for clinical trials and research to investigate the potential of immunotherapeutic treatment for melanoma. Increased knowledge of the tumor microenvironment as well as the biology of the human immune system and its pathways allows better, more improved therapeutic strategies. MAGE-A antigens, specific antigens present on melanoma tumor cells, indicate worse prognosis as well as lower rates of survival for melanoma patients. MAGE-A proteins promote aggressive cancer development, through affecting the p53 pathway, which is essential for cell growth regulation and apoptosis. Thus, MAGE-A presence on melanoma tumor cells is indicative of malignant phenotypes. Clinical studies indicate that intravenous administration of autologous genetically modified T-lymphocytes modified to express anti-MAGE-A3 antigen stimulate cellular and humoral immune responses, such as the production of antigen specific long term memory T cells, increased activity of effector T cells, disruption of interactions between the MAGE-A3 surface gene and the melanoma tumor cell, and increased frequency of anti-MAGE-A3 T lymphocytes in the blood. These immune responses all ultimately contribute to melanoma tumor regression. Clinical studies performed on a larger scale are needed to further verify these results. Lymphocytes genetically engineered to express anti-MAGE-A3 antigen provoke anti-propagating immune responses in malignant melanoma patients, demonstrating that they are the most effective form of immunotherapeutic treatment for malignant melanoma.


Keywords


Melanoma, Antigen, MAGE-A3, Immunotherapy, Lymphocyte, Immune, Treatment,

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