title: Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.
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-gamma 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-gamma 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.
authors.affiliation: The Ella Institute for Treatment and Research of Melanoma, Sheba Medical Center, Tel-Hashomer, Israel. michal.besser@sheba.health.gov.il
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Besser
authors.forename: Ronnie
authors.initials: R
authors.lastname: Shapira-Frommer
authors.forename: Avraham J
authors.initials: AJ
authors.lastname: Treves
authors.forename: Dov
authors.initials: D
authors.lastname: Zippel
authors.forename: Orit
authors.initials: O
authors.lastname: Itzhaki
authors.forename: Ester
authors.initials: E
authors.lastname: Schallmach
authors.forename: Adva
authors.initials: A
authors.lastname: Kubi
authors.forename: Bruria
authors.initials: B
authors.lastname: Shalmon
authors.forename: Izhar
authors.initials: I
authors.lastname: Hardan
authors.forename: Raphael
authors.initials: R
authors.lastname: Catane
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Sara
authors.initials: S
authors.lastname: Apter
authors.forename: Alon Ben
authors.initials: AB
authors.lastname: Nun
authors.forename: Iryna
authors.initials: I
authors.lastname: Kuchuk
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter