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

Flavio Arienti, Filiberto Belli, Filomena Napolitano, Josep Sulé-Suso, Arabella Mazzocchi, Gian Francesco Gallino, Alessandro Cattelan, Cristina Sanantonio, Licia Rivoltini, Cecilia Melani, Mario Paolo Colombo, Natale Cascinelli, Michele Maio, Giorgio Parmiani

Research output: Contribution to journalArticlepeer-review

Abstract

A human melanoma line genetically modified to release interleukin 4 (IL- 4) was utilized to immunize advanced melanoma patients in order to elicit or increase a specific anti-melanoma immune response, which may affect distant lesions. Twelve metastatic melanoma patients were injected subcutaneously at least three times with 5 x 107 IL-4 gene-transduced and irradiated allogeneic melanoma cells per dose. Both systemic and local toxicities were mild, consisting of transient fever and erythema, swelling, and induration at the vaccination site. Two mixed but not complete or partial clinical responses were recorded. To assess the immune response of vaccinated patients, both serological and cell-mediated activities were evaluated. Antibodies to alloantigens could be detected in 2 of 11 patients tested. Mixed tumor-lymphocyte cultures were performed, utilizing autologous and allogeneic HLA-A2-matched melanoma lines as simulators and targets. A significant increase in IFN-γ release was detected in 7 of 11 cases when postvaccination lymphocytes were stimulated by the untransduced allomelanoma cells. However, induction of a specific recognition of autologous melanoma cells by PBLs was obtained after vaccination in only one of six cases studied. This response involved the melanoma peptide Melan-A/MART-127-35 that was recognized in an HLA-A2-restricted fashion. These results indicate that vaccination with allogeneic melanoma cells releasing IL-4 locally can expand a T cell response against antigen(s) of autologous, untransduced tumor, although in a minority of patients.

Original languageEnglish
Pages (from-to)2907-2916
Number of pages10
JournalHuman Gene Therapy
Volume10
Issue number18
DOIs
Publication statusPublished - Dec 10 1999

ASJC Scopus subject areas

  • Genetics

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