Costimulation by CD48 and B7-1 induces immunity against poorly immunogenic tumors.
Genetic modification of many types of mouse tumors to express the B7-1 or B7-2 molecules, natural ligands for the T cell-costimulatory molecule CD28, increases their immunogenicity. However, even after transfection with the B7-1 and/or B7-2 genes, poorly immunogenic tumors fail to elicit and efficient immune response. We report here that two such tumors, the Ag104A sarcoma and the K1735-M2 melanoma, become immunogenic after transfection of the genes encoding murine B7-1 together with CD48, which is the natural ligand for CD2. Tumor-specific CD8+ cytotoxic T lymphocytes were readily generated and were effective for adoptive immunotherapy of metastasis induced by wild-type Ag104A sarcoma cells. A similar approach may be useful for developing therapy for other poorly immunogenic tumors, including those in humans.
Li
Y
Y
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Hellstrom
K E
KE
Newby
S A
SA
Chen
L
L
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D000071178:CD48 Antigen; D003001:Cloning, Molecular; D005260:Female; D005434:Flow Cytometry; D007114:Immunization; D016219:Immunotherapy, Adoptive; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D018448:Models, Immunological; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*; D015398:Signal Transduction; D014162:Transfection
D015703:Antigens, CD; D018122:B7-1 Antigen; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C000604066:Cd48 protein, mouse; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins