Mouse myeloma cell line secreting bifunctional fusion protein RM4/IFN-gamma [corrected] elicits antitumor CD8 MHC class I-restricted T cells that are cytolytic in vitro and tumoricidal in vivo.
Mouse myeloma cell line VKCK/RM4-IFN-gamma secreting the bifunctional fusion protein RM4/IFN-gamma was used to study the relationship between IFN-gamma secretion of tumor cells and its tumorigenicity and to study the potential mechanism responsible for the immune response. IFN-gamma secretion of VKCK/RM4-IFN-gamma tumor cells was estimated at 90 U/ml using an antiviral assay. To evaluate tumorigenicity, 5 x 10(5) viable IFN-gamma-secreting VKCK/RM4-IFN-gamma and non-IFN-gamma-secreting VKCK tumor cells were injected s.c. into syngeneic BALB/c mice and VKCK/RM4-IFN-gamma-immunized or T cell subset-depleted BALB/c mice, respectively. Tumor progression or regression was evaluated 2 weeks after tumor inoculation. Our animal studies showed that RM4/IFN-gamma secretion by VKCK/RM4-IFN-gamma tumor cells curtailed its tumorigenicity in BALB/c mice and induced a persistant protective immune response against a subsequent graft of parental VKCK tumor. This protective immunity is long term and tumor specific as measured in a 51Cr-release assay. In addition, our animal studies in T cell subset-depleted BALB/c mice showed that CD8 CTL play a major role in the reduction of tumorigenicity. This study thus highlights the potential advantages of localized IFN-gamma in tumors to induce potent antitumor immunity and further suggests that the bifunctional fusion protein RM4/IFN-gamma may be useful in cancer immunotherapy because of its capacity of targeting IFN-gamma to human tumors expressing the human tumor-associated TAG72 antigen [corrected].
Department of Microbiology, University of Saskatchewan, Saskatoon, Canada.
Y
Y
Qi
Y
Y
Chen
J
J
Xiang
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma