Anti-GD3 monoclonal antibody analysis of childhood T-cell acute lymphoblastic leukemia: detection of a target antigen for antibody-mediated cytolysis.
We have demonstrated in previous studies significant quantitative differences in the ganglioside content of leukemia cell membranes within immunological subclasses of acute lymphoblastic leukemia (ALL): The disialoganglioside GD3 (disialolactosylceramide) is increased in lymphoblasts with a T-cell immunophenotype compared to non-T-ALL blasts. Utilizing an indirect immunofluorescence assays with a monoclonal antibody to GD3(R24), pretreatment leukemic lymphoblasts from 80 children with ALL were assayed for GD3 expression. GD3 was observed in 75% of leukemic samples in which lymphoblasts exhibited a T-cell phenotype, whereas none of the 33 non-T-ALL samples tested exhibited GD3. Correlation between the expression of GD3 and various antigenic determinants of T-cell differentiation was restricted to CD2; 75% of CD2-negative T-cell ALL blasts failed to express GD3. Anti-GD3 immunoreactivity to T-ALL samples was not restricted to R24 in that two other monoclonal anti-GD3 antibodies were similarly reactive to T-ALL blasts. In vitro incubation of T-cell lymphoblasts with the anti-GD3 antibodies, R24 and C281 and human serum resulted in significant cytotoxicity, and R24 also mediated antibody-dependent cellular cytotoxicity by normal effector cells. Cytotoxicity was specific for those T-ALL blast cell populations which reacted with anti-GD3 as assessed by immunofluorescence microscopy. Since immunoreactivity with monoclonal antibody to GD3 was exclusively observed in a large population of immunophenotypically defined T-cell leukemic lymphoblasts, these studies suggest a possible immunodiagnostic and immunotherapeutic potential for anti-GD3 monoclonal antibodies in T-cell lymphoblastic malignancies.
Department of Hematology/Oncology, Children's National Medical Center, Washington, DC 20010.
G H
GH
Reaman
B J
BJ
Taylor
W D
WD
Merritt
D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis*; D002648:Child; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D005732:Gangliosides / Q000032:analysis* / Q000276:immunology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D005732:Gangliosides; C026226:ganglioside, GD3; D003165:Complement System Proteins