PT  - JOURNAL ARTICLE
AU  - Besser, Michal J.
AU  - Shapira-Frommer, Ronnie
AU  - Treves, Avraham J.
AU  - Zippel, Dov
AU  - Itzhaki, Orit
AU  - Hershkovitz, Liat
AU  - Levy, Daphna
AU  - Kubi, Adva
AU  - Hovav, Einat
AU  - Chermoshniuk, Natalia
AU  - Shalmon, Bruria
AU  - Hardan, Izhar
AU  - Catane, Raphael
AU  - Markel, Gal
AU  - Apter, Sara
AU  - Ben-Nun, Alon
AU  - Kuchuk, Iryna
AU  - Shimoni, Avichai
AU  - Nagler, Arnon
AU  - Schachter, Jacob
TI  - Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients
AID  - 10.1158/1078-0432.CCR-10-0041
DP  - 2010 May 01
TA  - Clinical Cancer Research
PG  - 2646--2655
VI  - 16
IP  - 9
4099  - http://clincancerres.aacrjournals.org/content/16/9/2646.short
4100  - http://clincancerres.aacrjournals.org/content/16/9/2646.full
SO  - Clin Cancer Res2010 May 01; 16
AB  - 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. Clin Cancer Res; 16(9); 2646–55. ©2010 AACR.