Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients

Michal J. Besser, Ronnie Shapira-Frommer, Avraham J. Treves, Dov Zippel, Orit Itzhaki, Liat Hershkovitz, Daphna Levy, Adva Kubi, Einat Hovav, Natalia Chermoshniuk, Bruria Shalmon, Izhar Hardan, Raphael Catane, Gal Markel, Sara Apter, Alon Ben-Nun, Iryna Kuchuk, Avichai Shimoni, Arnon Nagler, Jacob Schachter

Research output: Contribution to journalArticlepeer-review


Purpose: Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) has shown promising results in metastatic melanoma patients. Although objective response rates of over 50% have been reported, disadvantages of this approach are the labor-intensive TIL production and a very high drop-out rate of enrolled patients, limiting its widespread applicability. Previous studies showed a clear correlation between short TIL culture periods and clinical response. Therefore, we used a new TIL production technique using unselected, minimally cultured, bulk TIL (Young-TIL). The use of Young-TIL is not restricted to human leukocyte antigen (HLA)-A2 patients. The purpose of this study is to explore the efficacy and toxicity of adoptively transferred Young-TIL following lympho-depleting chemotherapy in metastatic melanoma patients, refractory to interleukin-2 and chemotherapy. Experimental Design: Young-TIL cultures for 90% of the patients were successfully generated, enabling the treatment of most enrolled patients. We report here the results of 20 evaluated patients. Results: Fifty percent of the patients achieved an objective clinical response according to the Response Evaluation Criteria in Solid Tumors, including two ongoing complete remissions (20+, 4+ months) and eight partial responses (progression-free survival: 18+, 13+, 10+, 9, 6+, 4, 3+, and 3 months). All responders are currently alive. Four additional patients showed disease stabilization. Side effects were transient and manageable. Conclusion: We showed that lympho-depleting chemotherapy followed by transfer of short-term cultured TIL can mediate tumor regression in 50% of metastatic melanoma with manageable toxicity. The convincing clinical results combined with the simplification of the process may thus have a major effect on cell therapy of cancer.

Original languageEnglish
Pages (from-to)2646-2655
Number of pages10
JournalClinical Cancer Research
Issue number9
StatePublished - 1 May 2010
Externally publishedYes


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