Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma.
In recent years, tumor immunotherapy has begun to exploit the emerging knowledge of the mechanisms of T cell activation to enhance the immune responses to tumors. However, many tumors, despite genetic modification to express co-stimulatory molecules or cytokines, are not readily rejected due to their inherently poor immunogenicity. In the present study, we tested whether expression of the co-stimulatory ligand B7-1 and the immunostimulatory cytokines interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by a mammary carcinoma (SM1) would sufficiently augment its immunogenicity to obtain rejection and immunity. Our findings demonstrate that expression of B7, IFN-gamma, or GM-CSF alone, or co-expression of B7 and GM-CSF did not result in rejection of SM1. However, co-expression of B7 and IFN-gamma was sufficient to result in regression of SM1 tumors by a CD8+ T cell-dependent mechanism. Rejection of the B7/IFN-gamma-expressing SM1 tumor resulted in protection from rechallenge not only with the unmodified SM1 tumor but with another syngeneic mammary tumor. Our data support the idea that although B7 expression alone may not be sufficient for rejection of certain tumors, the immune system may be stimulated to mount an effective anti-tumor immune response by the co-expression of both the co-stimulatory ligand and a cytokine.
Hurwitz
A A
AA
Howard Hughes Medical Institute, Cancer Research Laboratory, University of California, Berkeley 94720, USA. hurwitz@socrates.berkeley.edu
Townsend
S E
SE
Yu
T F
TF
Wallin
J A
JA
Allison
J P
JP
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002277:Carcinoma / Q000235:genetics* / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D018122:B7-1 Antigen; D007371:Interferon-gamma