New melanoma vaccine increases antitumor immunity

Vaccination with autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) engenders antitumor effects in patients with metastatic disease, according to the results of a phase I trial. The experimental vaccine uses an adenoviral vector that may have a better safety profile than earlier melanoma vaccine formulations.

Dr. Glenn Dranoff, of Dana-Farber Cancer Institute in Boston, and colleagues previously reported promising results for a similar vaccine strategy, in which gene transfer was mediated by a retrovirus. However, manufacturing the vaccine is complex and there are safety issues associated with use of retroviruses.”Using an adenoviral vector simplifies the manufacture of the vaccine, so what previously took a few months, can now be done in day or so,” Dr. Dranoff told Reuters Health. “And the safety profile, at least ex vivo, is quite good.”As his group reports in the September 1st issue of the Journal of Clinical Oncology, metastatic lesions were excised, dissociated into single cells, then transduced overnight with a replication-defective adenoviral vector encoding human GM-CSF. The investigators successfully prepared the vaccine for 34 of 35 patients. Preparations were irradiated prior to administration.Twenty-six patients completed at least one course of treatment, in which vaccine was injected at weekly and biweekly intervals, for a minimum of six doses. There were no significant major organ toxicities attributable to the vaccine, autoimmune reactions or adenoviral infections.The vaccine stimulated dendritic cell, macrophage and lymphocyte infiltrates in 19 of 26 patients, but eosinophil infiltrates were minimal compared with those engendered by retroviral-mediated gene transfer. “We think [the altered eosinophil response] relates to differences in the kinds of T cells that the two different vaccines generate, in terms of their production of cytokines like IL-5,” Dr. Dranoff explained.Ten of 16 patients developed significant lymphocyte infiltrates and tumor necrosis in distant metastases. Median survival for the whole cohort was 15 months. Ten patients survived for more than 36 months after study entry, and four had no evidence of disease after metastases were surgically removed.Dr. Dranoff commented that this type of vaccine strategy may benefit patients whose primary melanoma has spread to adjacent lymph nodes. But, he emphasized, this was a “preliminary, highly investigational study, and certainly should not be viewed in any way as standard treatment.” His group hopes to begin a phase II trial in the near future.(Source: J Clin Oncol 2003;21:3343-3350: Reuters Health: Karla Gale: September 10, 2003: Oncolink)