B7-1/CD80-transduced tumor cells elicit better systemic immunity than wild-type tumor cells admixed with Corynebacterium parvum.
Tumor cells genetically modified by transduction of B7 (B7-1/CD80), a natural ligand for the T-cell costimulatory molecules CD28 and CTLA-4, can elicit potent tumor immunity, and they can be effective for treatment of established cancers in animal models. In this study, three tumor lines, the EL4 lymphoma, the P815 mastocytoma, and the MCA102 sarcoma were transduced with recombinant retrovirus containing the murine B7 gene, and their potency to induce systemic immunity protective against challenge with wild-type tumor was compared to that of the same tumor cells admixed with the commonly used adjuvant Corynebacterium parvum. While admixture of tumor cells with C. parvum resulted in complete regression of tumors in syngeneic mice, it did not induce protective immunity against a subsequent challenge of wild-type cells from any of the 3 tumors tested. In contrast, B7-transduced EL4 and P815 tumors regressed locally and induced a potent systemic immunity to wild-type tumors and a higher level of cytotoxic T-cell activity than did tumor cells admixed with C. parvum. No systemic immunity was induced by B7-transduced nonimmunogenic MCA102 sarcoma cells. Our results demonstrate that immunogenic tumor cells transduced with the B7 gene are superior to tumor cells mixed with C. parvum for the induction of systemic tumor immunity.
Chen
L
L
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
McGowan
P
P
Ashe
S
S
Johnston
J V
JV
Hellström
I
I
Hellström
K E
KE
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D005260:Female; D018014:Gene Transfer Techniques; D007114:Immunization / Q000379:methods; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D008748:Methylcholanthrene; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011425:Propionibacterium acnes / Q000276:immunology*; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology*; D013945:Thymoma / Q000276:immunology*; D013953:Thymus Neoplasms / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D008748:Methylcholanthrene