Selective loss of expression of a tumor-associated antigen on a human leukemia cell line induced by treatment with monoclonal antibody and complement.
The sensitivity of a common acute lymphoblastic leukemia-associated antigen (cALLa)-positive, human leukemia pre-B-cell line to killing by antibody and complement was studied. A stable subpopulation was selected by its ability to survive four sequential treatments with excess monoclonal antibody (MoAb) directed against an Mr 24,000 glycoprotein associated with human leukemia cells and excess rabbit complement. Analysis of the antigen expression by individual cells within the parental and the selected cell populations was achieved by flow cytometry and demonstrated a marked decrease of the leukemia-associated antigen expression on individual cells within the selected subpopulation. These low-antigen-density cells were stable in subculture, and the immunoglobulin heavy-chain gene rearrangement of the parent population and the low-antigen-density subpopulation were identical, indicating that they were derived from a single cell source. The selection of this subpopulation was specific in that the expression of a second antigen recognized by a cALLa-specific MoAb was not affected. The presence of subpopulations of tumor cells with low levels of surface antigen expression that are resistant to killing upon addition of excess antibody and complement will prove to be an obstacle to the use of this approach to eliminate tumor cells from bone marrow that is to be used for autologous transplantation.
Gee
A P
AP
Bruce
K M
KM
van Hilten
J
J
Siden
E J
EJ
Braylan
R C
RC
Bauer
P C
PC
Boyle
M D
MD
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis*; D002460:Cell Line; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000276:immunology*; D008212:Lymphocyte Depletion; D009363:Neoplasm Proteins / Q000276:immunology; D012641:Selection, Genetic
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D009363:Neoplasm Proteins; D003165:Complement System Proteins