TY - JOUR T1 - Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules JF - Blood JO - Blood SP - 3515 LP - 3523 DO - 10.1182/blood-2005-03-1214 VL - 106 IS - 10 AU - Palena, Claudia AU - Foon, Kenneth A. AU - Panicali, Dennis AU - Yafal, Alicia Gómez AU - Chinsangaram, Jarasvech AU - Hodge, James W. AU - Schlom, Jeffrey AU - Tsang, Kwong Y. Y1 - 2005/11/15 UR - http://www.bloodjournal.org/content/106/10/3515.abstract N2 - Chronic lymphocytic leukemia (CLL) is a disease of CD5+ B lymphocytes (designated as CLL cells) that are inefficient antigen-presenting cells. Their poor ability to present antigens to the T cells, largely due to an inadequate costimulatory capacity, is manifested as a failure to stimulate proliferation of both allogeneic and autologous T cells. We have investigated the ability of in vitro manipulated CLL cells, via hyperexpression of a triad of costimulatory molecules (B7-1, intercellular adhesion molecule 1 [ICAM-1], and leukocyte-function–associated antigen 3 [LFA-3], designated TRICOM), to stimulate effective antitumor T-cell responses. A recombinant modified vaccinia virus strain Ankara (MVA), which is a highly attenuated, replication-impaired virus variant, was successfully used to infect and deliver the simultaneous expression of the 3 human costimulatory molecules in TRICOM on the surface of the CLL cells. Proliferation of allogeneic and autologous T cells was observed when MVA-TRICOM–infected CLL cells were used as stimulators in proliferation assays. Cytotoxic T lymphocytes, generated in vitro by stimulation of autologous T cells with MVA-TRICOM–infected CLL cells, showed cytotoxicity against unmodified/uninfected CLL cells. Therefore, our findings suggest that the use of CLL cells infected ex vivo with MVA-TRICOM or direct injection of MVA-TRICOM in patients with CLL has potential for the immunotherapy of CLL. ER -