Melanoma: The Promise of Immunotherapy

Immunotherapy, which is based on changes observed at the molecular level, presents an additional treatment option for melanoma that may result in better response rates and, possibly, a cure.

The recently approved antineoplastic agents ipilimumab and vemurafenib represent significant advances in melanoma treatment. However, side effects from these agents when used at FDA-approved doses are dose-limiting in approximately 10% of patients. Although these side effects can be managed, they tend to be more difficult to manage than those associated with traditional chemotherapy. Regardless, these drugs have completely changed the way melanoma is treated and have improved patient survival.

Immunotherapy, which is based on changes observed at the molecular level, presents an additional treatment option that may result in better response rates and, possibly, a cure. Genetic changes in certain small protein fragments are unique to melanoma cancer cells and may be targets for tumor-infiltrating lymphocytes that have been shown to reduce cancerous lesions. In an article published in the June 2013 issue of Nature Medicine, researchers reported they have developed a streamlined method to rapidly mine whole-exome sequence data that identifies mutated proteins expressed in melanoma tumors.

This research is based on a previous phase 2 clinical study that treated patients with self-donated tumor-infiltrating lymphocytes (white blood cells migrated into a tumor from the blood). In the study, 70% of patients experienced significant regression of metastatic lesions. Additionally, approximately 40% of patients had a durable response lasting 5 years or more. Patients who have many tumor-infiltrating lymphocytes are very likely mounting an immune response against their own tumors.

In light of these results, researchers need a method to quickly identify and quantify tumor-infiltrating lymphocytes. An efficient screening test could help identify which patients are the best candidates for immunotherapy. The technique developed for the Nature Medicine study uses next-generation DNA sequencing technologies to identify changes that create the unique protein fragments. This process should increase the effectiveness of patient-donated cell therapy and also potentially reveal novel tumor growth mechanisms.

The researchers report that this screening technique may extend to identifying mutated antigens in various tumor types in the future.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.