Differing from the above-cited studies using genetically modified tumor cells, Veelken et al. (119) in a pilot study applied IL-2-secreting allogeneic fibroblasts admixed with autologous tumor cells to 15 patients with advanced malignant tumors, including 6 melanoma patients. No major side effects were attributable to vaccines. In 2 melanoma patients, a dense infiltrate of both CD4+ and CD8+ T cells at vaccination sites was demonstrated. T cell lines generated from biopsies of these vaccination sites exhibited a dominant MHC class I-restricted cytotoxic activity against autologous tumor cells in vitro, and had identical V-D-J junctional sequence of TCR to that of infiltrating lymphocytes obtained from tumor sites of 1 patient. This suggests that the same CTL clone had infiltrated the tumor, circulated in the peripheral blood, and was amplified at the vaccination site (120).
At the Polish National Cancer Centers, a novel, mixed auto/ allogeneic cellular melanoma vaccine modified with the IL-6 and the sIL-6R genes was designed (121). Preclinical studies in a mouse model demonstrated that the IL-6/sIL-6R-based vaccine is able to elicit efficient antitumor responses, mediated by CD8 + and NK cells, which resulted in inhibition of the tumor growth, metastases formation, and prolonged survival of the animals treated. Irradiation of vaccine cells does not only lead to their sterilization, but also causes increased secretion of exogenous IL-6 and sIL-6R. Between January 1996 and November 1999, the Polish group has vaccinated more than 100 metastatic melanoma patients (stage III and IV). Promising clinical results in 41 patients with measurable disease [22% CR (5/41) +PR (4/41), 32% SD (13/41)], and the evidence of immune responses in the vaccinated patients—including the induction of vitiligo—have prompted the group to design a prospective-randomized clinical phase III trial in stage III and IV melanoma patients, which was opened in 2000 to recruit 220 patients across Poland. The disease-free interval and 2-year overall survival will be compared with an observation arm as primary endpoints (121).
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Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.