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

Abstract

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.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 9 Pg. 2646-55 (May 01 2010) ISSN: 1557-3265 [Electronic] United States
• PMID: 20406835 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 AACR.

Chemical References

• Interleukin-2

Topics

• Adult
• Aged
• Autoimmunity (immunology)
• Cells, Cultured
• Combined Modality Therapy
• Diarrhea (chemically induced)
• Female
• Follow-Up Studies
• Humans
• Immunotherapy, Adoptive (adverse effects, methods)
• Interleukin-2 (adverse effects, therapeutic use)
• Length of Stay
• Lymphocytes, Tumor-Infiltrating (immunology, pathology, transplantation)
• Male
• Melanoma (immunology, pathology, therapy)
• Middle Aged
• Neoplasm Metastasis
• Survival Analysis
• Time Factors
• Treatment Outcome