Vaccination of melanoma patients with interleukin 4 gene-transduced allogeneic melanoma cells

A human melanoma line genetically modified to release interleukin 4 (IL-4) was utilized to immunize advanced melanoma patients in order to elicit or i ncrease a specific anti-melanoma immune response, which may affect distant lesions. Twelve metastatic melanoma patients were injected subcutaneously a t least three times with 5 x 10(7) IL-4 gene-transduced and irradiated allo geneic melanoma cells per dose. Both systemic and local toxicities were mil d, consisting of transient fever and erythema, swelling, and induration at the vaccination site. Two mixed but not complete or partial:clinical respon ses were recorded. To assess the immune response of vaccinated patients, bo th serological and cell-mediated activities were evaluated. Antibodies to a lloantigens could be detected in 2 of 11 patients tested, Mixed tumor-lymph ocyte cultures were performed, utilizing autologous and allogeneic HLA-A2-m atched melanoma lines as simulators and targets. A significant increase in IFN-gamma release was detected in 7 of 11 cases when postvaccination lympho cytes were stimulated by the untransduced allomelanoma cells. However, indu ction of a specific recognition of autologous melanoma cells by PBLs was ob tained after vaccination in only one of six cases studied. This response in volved the melanoma peptide Melan-A/MART-1(27-35) that was recognized in an HLA-A2-restricted fashion. These results indicate that vaccination with al logeneic melanoma cells releasing IL-4 locally can expand a T cell response against antigen(s) of autologous, untransduced tumor, although in a minori ty of patients.