title: A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma.
abstract: This report describes a phase I clinical trial using nonmyeloablative, lympho-depleting chemotherapy in combination with adoptive immunotherapy in patients with metastatic melanoma. The chemotherapy-conditioning schedule that induced transient lymphopenia consisted of cyclophosphamide (30 or 60 mg/kg per day for 2 days) followed by fludarabine (25 mg/m(2) per day for 5 days). Immunotherapy for all patients consisted of in vitro expanded, tumor-reactive, autologous T-cell clones selected for high avidity recognition of melanoma antigens. Cohorts of three to six patients each received either no interleukin (IL)-2, low-dose IL-2 (72,000 IU/kg intravenously three times a day to a maximum of 15 doses), or high-dose IL-2 (720,000 IU/kg intravenously three times a day for a maximum of 12 doses). The toxicities associated with this treatment were transient and included neutropenia and thrombocytopenia that resolved in all patients. High dose intravenous IL-2 was better tolerated by patients after chemotherapy than during previous immunotherapy cycles without chemotherapy. No patient exhibited an objective clinical response to treatment, although five patients demonstrated mixed responses or transient shrinkage of metastatic deposits. This study established a nonmyeloablative-conditioning regimen that could be safely administered in conjunction with adoptive T-cell transfer and IL-2 in patients with metastatic melanoma.
authors: Surgery Branch, National Cancer Institute, Building 10, Room 2B08, 9000 Rockville Pike, Bethesda, MD 20892, USA. Mark_Dudley@nih.gov
authors: Mark E
authors: ME
authors: Dudley
authors: John R
authors: JR
authors: Wunderlich
authors: James C
authors: JC
authors: Yang
authors: Patrick
authors: P
authors: Hwu
authors: Douglas J
authors: DJ
authors: Schwartzentruber
authors: Suzanne L
authors: SL
authors: Topalian
authors: Richard M
authors: RM
authors: Sherry
authors: Francesco M
authors: FM
authors: Marincola
authors: Susan F
authors: SF
authors: Leitman
authors: Claudia A
authors: CA
authors: Seipp
authors: Linda
authors: L
authors: Rogers-Freezer
authors: Kathleen E
authors: KE
authors: Morton
authors: Azam
authors: A
authors: Nahvi
authors: Sharon A
authors: SA
authors: Mavroukakis
authors: Donald E
authors: DE
authors: White
authors: Steven A
authors: SA
authors: Rosenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D007376:Interleukin-2