Active immunization of metastatic melanoma patients with interleukin-2- transduced allogeneic melanoma cells: Evaluation of efficacy and tolerability

Filiberto Belli, Flavio Arienti, Josep Sulé-Suso, Claudio Clemente, Luigi Mascheroni, Alessandro Cattelan, Cristina Sanantonio, Gian Francesco Gallino, Cecilia Melani, Stefania Rao, Mario P. Colombo, Michele Maio, Natale Cascinelli, Giorgio Parmiani

Research output: Contribution to journalArticlepeer-review

Abstract

From January 1994 to July 1996 we immunized metastatic melanoma patients with HLA-A2-compatible, interleukin-2 (IL-2)-secreting, immunogenic melanoma lines in an attempt to induce a systemic reaction that might also affect distant melanoma lesions. Twelve patients (6 male and 6 female) aged from 28 to 72 years, affected with visceral and/or subcutaneous (s.c.) melanoma metastases, were treated. Two different HLA-A2+ melanoma lines were transduced with the human IL-2 gene (14932/IL-2 and 1 B6/IL-2) and used as vaccine. Two groups of 4 patients each were injected s.c. with 5 x 107 and 15 x 107 irradiated 14932/IL-2 melanoma cells respectively, whereas a third group received 5 x 107 cells of the second line (1 B6/IL-2). All patients received the vaccine on days 1, 13, 26: if no progression was evident, further immunizations were administered at monthly intervals. All patients were assessable for clinical response alter at least three injections of the vaccine. In 4 cases a stabilization of disease lasting from 2 to 6 months was observed; in 2 of them a mixed type of response to treatment was noted with simultaneous evidence of regressing and non-responding lesions in the same patients. No signs of clinical response were found in the remaining patients. Nine patients died of disease between 3 and 24 months alter the onset of therapy, whereas 3 were alive 3 months alter the end of therapy. The local and systemic side-effects of treatment were mild. These results indicate that vaccination with cells bearing the appropriate antigens and releasing IL-2 locally can produce weak clinical responses, but also indicate that better results may be achieved through modifications of the vaccine, the schedule of immunization and/or a more appropriate selection of patients.

Original languageEnglish
Pages (from-to)197-203
Number of pages7
JournalCancer Immunology, Immunotherapy
Volume44
Issue number4
DOIs
Publication statusPublished - 1997

Keywords

  • Gene therapy
  • Melanoma
  • Vaccination

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

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