Monoclonal antibody SN10 which shows a highly selective reactivity with human B leukemia-lymphoma and is effectively internalized into cells.
The monoclonal antibody termed SN10 (IgG1-k) which was generated and characterized in the present study shows a highly selective reactivity with fresh (uncultured) human leukemia-lymphoma cells. The antigen defined by SN10 is a cell surface glycoprotein composed of a single polypeptide chain of Mr 36,000 and designated as gp36. The primary reactivity of SN10 is against mature B-lineage leukemia-lymphoma cells. For instance, SN10 reacted with all of the 17 B non-Hodgkin's lymphoma specimens, all of the 15 B chronic lymphocytic leukemia specimens, both of the 2 B prolymphocytic leukemia specimens, all of the 3 B hairy cell leukemia specimens, and 2 of the 3 B acute lymphoblastic leukemia specimens tested. Of normal peripheral blood cells, only a marginal reactivity of SN10 was detected with a minor subpopulation (less than 1-4% among different specimens) of isolated B-cells from healthy donors. No significant reactivity of SN10 was detected against any other isolated normal peripheral blood cells which include T-cells, granulocytes, monocytes, erythrocytes, and platelets. Furthermore, no significant reactivity of SN10 was detected against normal bone marrow specimens. In immunohistological studies using frozen tissue sections, SN10 reacted well with malignant lymphomas and showed varying patterns of reaction with hyperplastic reactive lymph nodes. Various normal human tissues tested were unreactive with SN10. In general, glycoprotein 36 was more abundantly expressed on fresh (uncultured) leukemia-lymphoma cells than on cultured leukemia-lymphoma cell lines. No significant amount of circulating SN10 antigen was detected in the plasma of leukemia-lymphoma patients or normal healthy donors. Scatchard plot analysis of direct binding of radiolabeled SN10 to a fresh (uncultured) B non-Hodgkin's lymphoma cell specimen, a fresh B chronic lymphocytic leukemia cell specimen, and DND-39 (an American Burkitt's lymphoma cell line) showed equilibrium constants of 5.2, 5.8, and 6.8 x 10(8) liters/mol, respectively. Thus, SN10 shows a high binding avidity to each of the 3 B leukemia-lymphoma cell specimens tested. Ricin A chain conjugate of SN10 killed leukemia-lymphoma cells effectively, whereas the same conjugate showed no cytotoxicity against control cells. Thus, SN10 bound to target antigen on the cell surface was effectively internalized into the cell. The present results suggest the potential of SN10 for therapy as well as for diagnosis of various forms of leukemia-lymphoma, particularly mature B-lineage leukemia-lymphoma.
Takeuchi
T
T
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Barcos
M P
MP
Seon
B K
BK
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D015448:Leukemia, B-Cell / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008970:Molecular Weight; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D007074:Immunoglobulin G