17 Oct Dendritic Cell Vaccination May Help Uveal Melanoma
MedicalResearch.com Interview with:
Prof I. Jolanda M. de Vries
Professor, Dept of Tumor Immunology
Radboud University Nijmegen
Medical Research: What are the main findings of the study?
Prof. de Vries: Dendritic cells are antigen-presenting cells with the unique capacity to activate naive antigen-specific T cells, and by this means are very suitable to induce immunologic antitumor responses. Dendritic cells cultured from monocytes can be matured and loaded with tumor antigen ex vivo and administered back into the patient. Within the lymph node, dendritic cells present antigens to T cells to initiate an immune response.
Metastatic uveal melanoma patients were vaccinated with autologous DCs loaded with tumor antigens (gp100 and tyrosinase), obtained by leukapheresis, according to a schedule of 3 biweekly vaccinations. One to 2 weeks after the last vaccination, a skin test was performed to analyse the induction of immunologic responses.
We can conclude that dendritic cell vaccination is feasible and safe in metastatic uveal melanoma. Dendritic cell-based immunotherapy is potent to enhance the host’s antitumor immunity against uveal melanoma in approximately one third of patients.
Medical Research: What was most surprising about the results?
Prof. de Vries: Although the primary end point of the dendritic cell vaccination studies was safety and feasibility; the most surprising result was the data on overall survival. The median overall survival of the vaccinated metastatic uveal melanoma patients was 19.2 months, not only exceeding the overall survival as reported in studies using systemic treatment, but also the overall survival in almost all studies in more selected metastatic uveal melanoma patients treated with local therapies of the liver.
Medical Research: What should clinicians and patients take away from your report?
Prof. de Vries: Uveal melanoma is a rare disease and therefore patients are often excluded from clinical trials for metastatic melanoma patients. This is almost certainly justified in the case of targeted therapies, e.g. with the absence of BRAF mutations in uveal melanoma, BRAF inhibitors are unlikely to have clinically meaningful benefit. To the contrary, uveal melanoma does have many overlapping immunological features with cutaneous melanoma, despite developing in the immune privileged environment of the eye. Therefore, patients might benefit just as much as patients with cutaneous melanoma from different sorts of immunotherapy.
Medical Research: What recommendations do you have for future research as a result of this study?
Prof. de Vries: Successful treatment of metastatic uveal melanoma has proven to be extremely hard and to date; no adjuvant therapy has shown survival benefit. Because immunologic responses after dendritic cell vaccination are induced more frequently in patients before clinically detectable metastasis develop, research in the near future should explore the possibilities of dendritic cell vaccination, and other immunotherapies, in the adjuvant setting of uveal melanoma.