Adoptive Cell Transfer and Lymphodepleting Chemotherapy for the Treatment of Metastatic Melanoma

Introduction: Malignant melanoma, the most aggressive of all skin cancers, is on the increase throughout the world. Melanoma is a malignant tumor of melanocytes predominately of skin, but also found in the digestive tract and eye. Its occurrence is statistically less than other forms of skin cancer, but corresponds to the highest mortality. Surgical resection, in its early stages, is the only proven curative treatment. Metastatic disease is incurable in most patients due to its refractibility to systemic cancer treatment. There are currently a large number of treatment regimens in clinical use, and also ongoing clinical trials. The problem with currently available regimens relates to the high cost and relative toxicities. However, in the last decade, trials utilizing adoptive transfer of lymphocytes after host lymphodepletion via chemotherapy, have demonstrated objective cancer regression in human patients with metastatic melanoma. Methods: The focus of this study was to review the current literature for the last 10 years on all studies pertaining to Adoptive Cell Transfer in treating metastatic melanoma. Electronic databases (Ovid – Medline, Pub-Med, MD Consult, NIH) were utilized. There were no gender or age restrictions. Only studies published in English were reviewed. Results: Four clinical studies were chosen for this review in which patients with refractory metastatic malignant melanoma were treated with varying doses of lymphdepleting chemotherapy and ACT. Variables within each study were manipulated as to ascertain response changes, but the primary treatment remained the same. Favorable clinical response was observed in a minority of patients in each study, but because of the experimental nature of this method of treatment, overall outcomes continue to fluctuate. Conclusion: This new form of epithelial cancer treatment is just in its infancy. With each consecutive research trial, advances continue to be made. Melanoma is the deadliest of all skin cancers. With advances being made daily in cellular engineering, it is only a matter of time before we have an effective form of ACT treatment for malignant melanoma