Role of B7-1 in mediating an immune response to myeloid leukemia cells.
A costimulatory signal from B7-1 (CD80) to its counter-receptor CD28 is required for T-cell activation. Many tumors, including most human leukemias, lack expression of B7-1, and this has been suggested to contribute to the failure of immune recognition of these diseases. A murine leukemia model system was developed to assess the potential role of B7-1 in the induction immunity to leukemia cells. The nonleukemic 32Dc13 myeloid cell line was transformed by transfection of the BCR/ABL gene, generating a subline (32Dp210/clone 26) that was leukemic and rapidly lethal to syngeneic, immunocompetent C3H/HeJ mice or T-cell-deficient nude mice. B7-1-modified leukemic cells remained lethal in nude mice, but caused only a transient, nonlethal leukemia in C3H/HeJ mice. After a single exposure to live, nonirradiated B7-1-modified leukemic cells, C3H/HeJ mice developed protective immunity against subsequent challenge with B7-1(-) leukemic cells. Further, hyperimmunization with B7-1(+) leukemic cells prolonged the survival of mice previously injected with a lethal number of B7-1(-) leukemic cells. These results indicate that myeloid leukemic cells may be attractive candidates for B7-1 gene transfer.
Matulonis
U A
UA
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Dosiou
C
C
Lamont
C
C
Freeman
G J
GJ
Mauch
P
P
Nadler
L M
LM
Griffin
J D
JD
D000208:Acute Disease; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D001854:Bone Marrow Cells; D018106:CD28 Antigens / Q000502:physiology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology; D007121:Immunocompetence; D007167:Immunotherapy; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000637:transplantation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D018122:B7-1 Antigen; D018106:CD28 Antigens; D011993:Recombinant Fusion Proteins; D016044:Fusion Proteins, bcr-abl