Treatment of patients with progressive unresectable metastatic melanoma with a heterologous polyvalent melanoma whole cell vaccine

Abstract

Unresectable metastatic melanoma has no elective treatment. Neither chemotherapy, intravenous IL-2 nor biochemotherapy clearly improves the overall survival. Recent assays with therapeutic vaccines have been recently yielded promising results. Here, we describe the application, clinical tolerance and antitumoural activity of a heterologous polyvalent melanoma whole cell vaccine in patients with metastatic melanoma. Twenty-eight AJCC stage III/IV melanoma patients with progressive unresectable metastatic disease were treated with our heterologous polyvalent melanoma whole cell vaccine between July 1, 1998 and July 1, 2002. All patients had already been unsuccessfully treated with high doses of IFN-␣2 and/or polychemotherapy and/or biochemotherapy and/or perfusion of extremities, or could not receive other treatments due to their age or underlying illness. Twenty-three were assessable. The vaccine was constituted by 10 melanoma cell lines, derived from primary, lymph node and metastatic melanomas. Prior to intradermal inoculation, the cells were irradiated and mixed with BCG, and 50% were treated with DNFB. After a median follow-up of 19 months, 26% of patients responded: 3 CR (18, 16؉, and 26؉ months), 2 PR (8 and 22 months) and 1 MR (36؉ months). The median survival of the whole group was 20.2 months. None of the 28 patients initially included in the study presented significant toxicity. This vaccination program had specific antitumoural activity in advanced metastatic melanoma patients and was well tolerated. The clinical responses and the median survival of our group of patients, together with the low toxicity of our polyvalent vaccine, suggest that this approach could be applied to earlier metastatic melanoma patients.

Delayed Disease Progression after Allogeneic Cell Vaccination in Hormone-Resistant Prostate Cancer and Correlation with Immunologic Variables

“…The use of allogeneic irradiated whole tumor cells has clear advantages in terms of vaccine production, and obviates the need to procure autologous tumor tissue and generate bespoke vaccine. Considerable clinical data exists for the use of allogeneic whole cell vaccines, particularly in melanomas (14,15,31). This approach is further supported by recent observations that crosspriming of CD8+ T cells is based on the transfer of proteasome substrates rather than peptides.…”

Overview of Tumor Cell–Based Vaccines

“…In one study, a mixture of 10 cell lines plus BCG was used to vaccinate metastatic melanoma patients [26]. Six of 23 patients responded to the vaccine (three complete responses, two partial responses, and one mixed response) and had a median survival of 20.2 months.…”

“…This highlights the need for careful selection of cell lines used in allogeneic vaccines to match the antigenic profile of the patient. However, as the principle of whole-cell vaccination is based on targeting of unknown epitopes, many such vaccines are composed of a mixture of several cell lines that are hoped to give the best antigenic spread [23][24][25][26].…”

Melanoma of the head and neck

“…This study [17] identified an improvement in median and overall 5-year survival in the vaccine therapy group over controls. In a study of unresectable, metastatic melanoma patients, a heterologous polyvalent melanoma whole cell vaccine developed from melanoma cell lines was administered resulting in three complete responder patients and two partial responder patients [66]. In another large study [67] of 214 melanoma patients (tumor-free following lymphadenectomy) with stage III disease using a vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), and treated with low-dose cyclophosphamide, there was a 44% 5-year survival.…”