Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules.
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.
Palena
Claudia
C
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Foon
Kenneth A
KA
Panicali
Dennis
D
Yafal
Alicia Gómez
AG
Chinsangaram
Jarasvech
J
Hodge
James W
JW
Schlom
Jeffrey
J
Tsang
Kwong Y
KY
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus
D015703:Antigens, CD; D019496:Cancer Vaccines