OBJECTIVES: To determine the feasibility and toxicity of the adoptive transfer of ex vivo-activated T lymphocytes that have been sensitized to autologous tumor vaccine in vivo. METHODS: Twenty patients with extensive metastatic renal cell carcinoma received systemic adoptive immunotherapy with autologous T cells in the absence of conjunctional interleukin-2 (IL-2) administration. Patients were vaccinated 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 removed, and the cells were stimulated with staphylococcal enterotoxin A followed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulated with anti-CD3 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 doses ranging from 2x10(9) to 9.5x10(10). There was minimal toxicity consisting of grade 1 or 2 fever and nausea, and the entire treatment was delivered as outpatient therapy. One patient had a partial response, one had a mixed response, and 8 had stable disease lasting at least 5 months. CONCLUSIONS: Adoptive transfer of ex vivo-activated, tumor vaccine-primed lymph node cells is feasible and is associated with minimal toxicity when used alone. These results warrant further study in a Phase II trial.
OBJECTIVES: To determine the feasibility and toxicity of the adoptive transfer of ex vivo-activated T lymphocytes that have been sensitized to autologous tumor vaccine in vivo. METHODS: Twenty patients with extensive metastatic renal cell carcinoma received systemic adoptive immunotherapy with autologous T cells in the absence of conjunctional interleukin-2 (IL-2) administration. Patients were vaccinated 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 removed, and the cells were stimulated with staphylococcal enterotoxin A followed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulated with anti-CD3 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 doses ranging from 2x10(9) to 9.5x10(10). There was minimal toxicity consisting of grade 1 or 2 fever and nausea, and the entire treatment was delivered as outpatient therapy. One patient had a partial response, one had a mixed response, and 8 had stable disease lasting at least 5 months. CONCLUSIONS: Adoptive transfer of ex vivo-activated, tumor vaccine-primed lymph node cells is feasible and is associated with minimal toxicity when used alone. These results warrant further study in a Phase II trial.
Authors: Chengwen Liu; Carol M Lewis; Yanyan Lou; Chunyu Xu; Weiyi Peng; Yan Yang; Alexander H Gelbard; Gregory Lizée; Dapeng Zhou; Willem W Overwijk; Patrick Hwu Journal: J Immunother Date: 2012-04 Impact factor: 4.456
Authors: Yanyan Lou; Gang Wang; Gregory Lizée; Grace J Kim; Steven E Finkelstein; Chiguang Feng; Nicholas P Restifo; Patrick Hwu Journal: Cancer Res Date: 2004-09-15 Impact factor: 12.701
Authors: Li-Xin Wang; Wen-Xin Huang; Hallie Graor; Peter A Cohen; Julian A Kim; Suyu Shu; Gregory E Plautz Journal: J Transl Med Date: 2004-11-26 Impact factor: 5.531