T-cell adoptive immunotherapy of metastatic renal cell carcinoma

Objectives. To determine the feasibility and toxicity of the adoptive trans fer of ex vivo-activated T lymphocytes that have been sensitized to autolog ous tumor vaccine in vivo. Methods. Twenty patients with extensive metastatic renal cell carcinoma rec eived systemic adoptive immunotherapy with autologous T cells in the absenc e of conjunctional interleukin-2 (IL-2) administration. Patients were vacci nated intradermally with irradiated autologous tumor cells and granulocyte- macrophage colony-stimulating factor as an adjuvant to stimulate an immune response. Inguinal lymph nodes draining the vaccine site were surgically re moved, and the cells were stimulated with staphylococcal enterotoxin A foll owed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulat ed with anti-CDS monoclonal antibody and IL-2, to obtain a large number of cells. Results. The staphylococcal enterotoxin A/IL-2 activation induced vigorous proliferation of T cells (median expansion 26-fold) that were a mixture of CD4 and CD8 T lymphocytes. Activated cells were infused intravenously at do ses ranging from 2 x 10(9) to 9.5 x 10(10). There was minimal toxicity cons isting of grade 1 or 2 fever and nausea, and the entire treatment was deliv ered as outpatient therapy. One patient had a partial response, one had a m ixed response, and 8 had stable disease lasting at least 5 months. Conclusions. Adoptive transfer of ex vivo-activated, tumor vaccine-primed l ymph node cells is feasible and is associated with minimal toxicity when us ed alone. These results warrant further study in a Phase II trial. UROLOGY 54: 617-624, 1999. (C) 1999, Elsevier Science Inc.