PURPOSE: Xcellerated T Cells (Xcyte Therapies, Seattle, WA) are autologous T cells that have been activated and expanded ex vivo using antibodies to CD3 and CD28 coimmobilized on magnetic beads. This study assessed the safety, immunostimulatory effects, and antitumor activity of Xcellerated T Cells and interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Twenty-six patients with measurable metastatic RCC after prior nephrectomy underwent leukapheresis. Peripheral blood lymphocytes were stimulated ex vivo for 8 days. Two cycles of therapy separated by 28 days were planned, with each cycle consisting of i.v. Xcellerated T Cells on day 1 and s.c. IL-2 at 10 x 10(6) units on days 1-10. RESULTS: Forty-nine cycles of therapy were administered to 25 patients. A mean (+/-SD) of 21.8 x 10(9) (+/-5.4 x 10(9)) Xcellerated T Cells were administered each cycle. The infused cells were 94% +/- 3% CD3(+), 64 +/- 12% CD4(+), and 25 +/- 12% CD8(+) (mean +/- SD). Adverse events (most commonly, fever and an influenza-like syndrome) were mild to moderate. Two patients developed significantly elevated human antimouse antibody titers (HAMA). No complete or partial clinical responses were observed. However, two patients experienced significant tumor regression in bone metastases. Median survival was 21 months. The number of cells infused correlated with the peak absolute lymphocyte count achieved, and there was a trend to increased postinfusion survival in patients achieving higher peak absolute lymphocyte counts. CONCLUSIONS: Adoptive immunotherapy with Xcellerated T Cells and IL-2 can be carried out safely on an outpatient basis in patients with advanced RCC. Further investigation of this therapy is warranted.
PURPOSE: Xcellerated T Cells (Xcyte Therapies, Seattle, WA) are autologous T cells that have been activated and expanded ex vivo using antibodies to CD3 and CD28 coimmobilized on magnetic beads. This study assessed the safety, immunostimulatory effects, and antitumor activity of Xcellerated T Cells and interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Twenty-six patients with measurable metastatic RCC after prior nephrectomy underwent leukapheresis. Peripheral blood lymphocytes were stimulated ex vivo for 8 days. Two cycles of therapy separated by 28 days were planned, with each cycle consisting of i.v. Xcellerated T Cells on day 1 and s.c. IL-2 at 10 x 10(6) units on days 1-10. RESULTS: Forty-nine cycles of therapy were administered to 25 patients. A mean (+/-SD) of 21.8 x 10(9) (+/-5.4 x 10(9)) Xcellerated T Cells were administered each cycle. The infused cells were 94% +/- 3% CD3(+), 64 +/- 12% CD4(+), and 25 +/- 12% CD8(+) (mean +/- SD). Adverse events (most commonly, fever and an influenza-like syndrome) were mild to moderate. Two patients developed significantly elevated human antimouse antibody titers (HAMA). No complete or partial clinical responses were observed. However, two patients experienced significant tumor regression in bone metastases. Median survival was 21 months. The number of cells infused correlated with the peak absolute lymphocyte count achieved, and there was a trend to increased postinfusion survival in patients achieving higher peak absolute lymphocyte counts. CONCLUSIONS: Adoptive immunotherapy with Xcellerated T Cells and IL-2 can be carried out safely on an outpatient basis in patients with advanced RCC. Further investigation of this therapy is warranted.
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: Raquel Gomez-Eerland; Bastiaan Nuijen; Bianca Heemskerk; Nienke van Rooij; Joost H van den Berg; Jos H Beijnen; Wolfgang Uckert; Pia Kvistborg; Ton N Schumacher; John B A G Haanen; Annelies Jorritsma Journal: Hum Gene Ther Methods Date: 2014-09-22 Impact factor: 2.396
Authors: Renier J Brentjens; Isabelle Rivière; Jae H Park; Marco L Davila; Xiuyan Wang; Jolanta Stefanski; Clare Taylor; Raymond Yeh; Shirley Bartido; Oriana Borquez-Ojeda; Malgorzata Olszewska; Yvette Bernal; Hollie Pegram; Mark Przybylowski; Daniel Hollyman; Yelena Usachenko; Domenick Pirraglia; James Hosey; Elmer Santos; Elizabeth Halton; Peter Maslak; David Scheinberg; Joseph Jurcic; Mark Heaney; Glenn Heller; Mark Frattini; Michel Sadelain Journal: Blood Date: 2011-08-17 Impact factor: 22.113
Authors: Bruno Nervi; Michael P Rettig; Julie K Ritchey; Hanlin L Wang; Gerhard Bauer; Jon Walker; Mark L Bonyhadi; Ronald J Berenson; Julie L Prior; David Piwnica-Worms; Jan A Nolta; John F DiPersio Journal: Exp Hematol Date: 2007-08-30 Impact factor: 3.084
Authors: Jonathan M Weiss; W Gregory Alvord; Octavio A Quiñones; Jimmy K Stauffer; Robert H Wiltrout Journal: Hum Immunol Date: 2014-05-04 Impact factor: 2.850