RT Journal Article
SR Electronic
T1 Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 2646
OP 2655
DO 10.1158/1078-0432.CCR-10-0041
VO 16
IS 9
A1 Besser, Michal J.
A1 Shapira-Frommer, Ronnie
A1 Treves, Avraham J.
A1 Zippel, Dov
A1 Itzhaki, Orit
A1 Hershkovitz, Liat
A1 Levy, Daphna
A1 Kubi, Adva
A1 Hovav, Einat
A1 Chermoshniuk, Natalia
A1 Shalmon, Bruria
A1 Hardan, Izhar
A1 Catane, Raphael
A1 Markel, Gal
A1 Apter, Sara
A1 Ben-Nun, Alon
A1 Kuchuk, Iryna
A1 Shimoni, Avichai
A1 Nagler, Arnon
A1 Schachter, Jacob
YR 2010
UL http://clincancerres.aacrjournals.org/content/16/9/2646.abstract
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.