Adjuvant immunotherapy with tumor infiltrating lymphocytes and interleukin-2 in patients with resected stage III and IV melanoma

Laura Ridolfi, Ruggero Ridolfi, Angela Riccobon, Franca De Paola, Massimiliano Petrini, Monica Stefanelli, Emanuela Flamini, Alessandra Ravaioli, Giorgio Maria Verdecchia, Giusto Trevisan, Dino Amadori

Research output: Contribution to journalArticle

Abstract

Adoptive immunotherapy with tumor infiltrating lymphocytes (TIL) and interleukin (IL)-2 is reasonably effective in the treatment of patients with advanced melanoma. However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stage's (resected stages III and IV). In a preliminary study, 25 patients (aged 23-72 years) with stage III-IV melanoma who underwent resection of metachronous metastases were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 106 IU/m2) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) evaluable patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) rates were 44% and 37%, respectively, at 2 years, and 52% and 45% at 3 years. The CNS was the only site of disease recurrence in 57% of patients who relapsed. DF patients received a higher median dose of IL-2 than those who progressed (total dose 110 x 106 versus 86 x 106 IU/m2, respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. Analysis of tumor immunosuppression factors in lymphocytes inside the tumor (TCR ζ and ε chains, p56Ick, FAS, and FAS-ligand) confirmed that the immunologic potential of TIL, depressed at the time of metastasectomy, was significantly restored after in vitro culture with IL-2. Adoptive immunotherapy with TIL and IL-2 could improve DFS and OS, although further work is required to determine its role in the treatment of patients with high-risk melanoma.

Original languageEnglish
Pages (from-to)156-162
Number of pages7
JournalJournal of Immunotherapy
Volume26
Issue number2
DOIs
Publication statusPublished - Mar 2003

Keywords

  • Interleukin-2
  • Melanoma
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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  • Cite this

    Ridolfi, L., Ridolfi, R., Riccobon, A., De Paola, F., Petrini, M., Stefanelli, M., Flamini, E., Ravaioli, A., Verdecchia, G. M., Trevisan, G., & Amadori, D. (2003). Adjuvant immunotherapy with tumor infiltrating lymphocytes and interleukin-2 in patients with resected stage III and IV melanoma. Journal of Immunotherapy, 26(2), 156-162. https://doi.org/10.1097/00002371-200303000-00008