Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma
Autor: | Nicholas P. Schaub, James Chih-Hsin Yang, Richard M. Sherry, Udai S. Kammula, Robert Somerville, Nicholas P. Restifo, Steven A. Rosenberg, Seth M. Steinberg, Donald E. White, Debbie Ann N. Nathan, Colin A. Gross, Carolyn M. Laurencot, Giao Q. Phan, Rosati Shannon Faith, Young Hong, Michael S. Hughes, Mark E. Dudley, John R. Wunderlich |
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Rok vydání: | 2013 |
Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Adolescent medicine.medical_treatment chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Immunotherapy Adoptive Cell therapy Interferon-gamma Young Adult Lymphocytes Tumor-Infiltrating Internal medicine medicine Tumor Cells Cultured Humans Prospective Studies Prospective cohort study Child Melanoma Aged Chemotherapy Tumor-infiltrating lymphocytes business.industry hemic and immune systems Immunotherapy Middle Aged medicine.disease Clinical trial Response Evaluation Criteria in Solid Tumors Immunology Interleukin-2 Female business |
Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 31(17) |
ISSN: | 1527-7755 |
Popis: | Purpose Adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) and high-dose interleukin-2 (IL-2) administered to lymphodepleted patients with melanoma can cause durable tumor regressions. The optimal TIL product for ACT is unknown. Patients and Methods Patients with metastatic melanoma were prospectively assigned to receive unselected young TILs versus CD8+-enriched TILs. All patients received lymphodepleting chemotherapy and high-dose IL-2 therapy and were assessed for response, toxicity, survival, and immunologic end points. Results Thirty-four patients received unselected young TILs with a median of 8.0% CD4+ lymphocytes, and 35 patients received CD8+-enriched TILs with a median of 0.3% CD4+ lymphocytes. One month after TIL infusion, patients who received CD8+-enriched TILs had significantly fewer CD4+ peripheral blood lymphocytes (P = .01). Twelve patients responded to therapy with unselected young TILs (according to Response Evaluation Criteria in Solid Tumors [RECIST]), and seven patients responded to CD8+-enriched TILs (35% v 20%; not significant). Retrospective studies showed a significant association between response to treatment and interferon gamma secretion by the infused TILs in response to autologous tumor (P = .04), and in the subgroup of patients who received TILs from subcutaneous tumors, eight of 15 patients receiving unselected young TILs responded but none of eight patients receiving CD8+-enriched TILs responded. Conclusion A randomized selection design trial was feasible for improving individualized TIL therapy. Since the evidence indicates that CD8+-enriched TILs are not more potent therapeutically and they are more laborious to prepare, future studies should focus on unselected young TILs. |
Databáze: | OpenAIRE |
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