Analysis of cytolytic effector cell response in vitro against autologous human tumor cells genetically altered to synthesize interleukin-2.
Recently, there has been a surge of interest in gene therapy in cancer particularly with cytokine transduced tumor cells as a novel form of tumor vaccine. In two autologous human tumor systems, using the tumor cells engineered to produce interleukin-2 by gene transduction techniques, we have examined whether or not such genetically altered cells are capable of inducing a tumor specific cytolytic T cell (CTL) response, in vitro, in co-culture with the respective autologous peripheral blood lymphocytes (PBL). We found that in neither system did co-cultures of the IL-2 producing tumor cells and the autologous PBL generate much cytolytic effector cell activity directed against the respective tumor cells, although these co-cultures did lead to the generation of substantial levels of natural killer (NK) cell activity when measured against the prototype NK sensitive target K562 line. More surprisingly, the levels of lymphokine activated killer cell responses against the respective autologous targets that could be generated in the PBL with exogenous IL-2 alone were compromised by the presence of the autologous tumor cells in the co-culture.
Tohmatsu
A
A
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030.
Okino
T
T
Stabach
P
P
Padula
S J
SJ
Ergin
M T
MT
Mukherji
B
B
D000951:Antigens, Neoplasm; D001324:Autoantigens; D003602:Cytotoxicity, Immunologic; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D007519:Isoantigens; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000951:Antigens, Neoplasm; D001324:Autoantigens; D007376:Interleukin-2; D007519:Isoantigens