TY - JOUR
T1 - A Phase I Study of Nonmyeloablative Chemotherapy and Adoptive Transfer of Autologous Tumor Antigen-Specific T Lymphocytes in Patients With Metastatic Melanoma
AU - Dudley, Mark E.
AU - Wunderlich, John R.
AU - Yang, James C.
AU - Hwu, Patrick
AU - Schwartzentruber, Douglas J.
AU - Topalian, Suzanne L.
AU - Sherry, Richard M.
AU - Marincola, Francesco M.
AU - Leitman, Susan F.
AU - Seipp, Claudia A.
AU - Rogers-Freezer, Linda
AU - Morton, Kathleen E.
AU - Nahvi, Azam
AU - Mavroukakis, Sharon A.
AU - White, Donald E.
AU - Rosenberg, Steven A.
PY - 2002
Y1 - 2002
N2 - 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 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.
AB - 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 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.
KW - Adoptive transfer therapy
KW - Interleukin-2 therapy
KW - Melanoma
KW - Nonmyeloablative chemotherapy
KW - T-cell clones
UR - http://www.scopus.com/inward/record.url?scp=18344362786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18344362786&partnerID=8YFLogxK
U2 - 10.1097/00002371-200205000-00007
DO - 10.1097/00002371-200205000-00007
M3 - Article
C2 - 12000866
AN - SCOPUS:18344362786
SN - 1524-9557
VL - 25
SP - 243
EP - 251
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
IS - 3
ER -