Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients

Michal J. Besser, Ronnie Shapira-Frommer, Avraham J. Treves, Dov Zippel, Orit Itzhaki, Ester Schallmach, Adva Kubi, Bruria Shalmon, Izhar Hardan, Raphael Catane, Eran Segal, Gal Markel, Sara Apter, Alon Ben Nun, Iryna Kuchuk, Avichai Shimoni, Arnon Nagler, Jacob Schachter

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-γ upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-γ selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Original languageEnglish
Pages (from-to)415-423
Number of pages9
JournalJournal of Immunotherapy
Volume32
Issue number4
DOIs
StatePublished - 1 May 2009
Externally publishedYes

Keywords

  • Adoptive cell therapy
  • Interleukin-2
  • Melanoma
  • Tumor-infiltrating lymphocytes

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