Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2

Flavio Arienti, Filiberto Belli, Licia Rivoltini, Carlo Gambacorti-Passerini, Luigi Furlan, Luigi Mascheroni, Augusto Prada, Maurilia Rizzi, Edoardo Marchesi, Maurizio Vaglini, Giorgio Parmiani, Natale Cascinelli

Research output: Contribution to journalArticlepeer-review

Abstract

Freshly isolated tumor-infiltrating lymphocytes (TIL) from stage IV melanoma patients were cultured for 2 weeks with low doses of interleukin-2 (IL-2; 120 IU/ml), to select potentially for tumor-specific lymphocytes present in the neoplastic lesion, followed by high doses (6000 IU/ml) to achieve lymphocyte expansion. TIL were serially analyzed for their expansion, phenotype and cytotoxic activity against autologous and allogeneic tumor cells. A preferential lysis of autologous melanoma cells was obtained in long-term cultures of 7/13 cases (54%), while the remaining ones showed a major-histocompatibility-complex-unrestricted, lymphokine-activated-killer(LAK)-like activity at the time of in vivo injection. Sixteen patients with metastatic melanoma were infused with TIL (mean number: 6.8×109, range: 0.35 × 109-20 × 109) and IL-2 (mean dose: 130 × 106 IU, range: 28.8 × 106-231 × 106 IU); 1 complete and 3 partial responses were observed in 12 evaluable patients (response rate 33%). In all responding patients, injected TIL showed an in vitro preferential lysis of autologous tumor cells, while in no cases were TIL with LAK-like activity associated with a clinical response. The mean autologous tumor cytotoxic activity of TIL at the time of in vivo injection was significantly higher in responding patients in comparison to nonresponding ones, suggesting that a marked and preferential cytolysis of autologous tumor cells is associated with the therapeutic efficacy of TIL.

Original languageEnglish
Pages (from-to)315-322
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume36
Issue number5
DOIs
Publication statusPublished - Sep 1993

Keywords

  • Immunotherapy
  • Interleukin-2
  • Melanoma
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

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