Our overall objectives remain to be the immunological and biochemical characterization of human leukemia-lymphoma (HLL)-associated cell membrane antigens and the preparation of specific anti-HLL antibody reagents for clinical use as well as for immunochemical studies of human malignant lymphoreticular cells. In addition to our previously described monoclonal antibody (mAb) SN1 directed to a unique human T-cell leukemia antigen, termed TALLA, we have generated monoclonal antibodies, termed SN2, SN2a, and SN2b, that define a human T-cell leukemia-associated cell surface glycoprotein, GP37, with an approximate Mr = 37,000. These antibodies were generated by using a human leukemia antigen preparation. The reactivity and specificity of these monoclonal antibodies (mAbs) were characterized by a sensitive radioimmunoassay against a variety of cultured and uncultured human cells. In selected cases, the cell specimens were further tested by indirect immunofluorescence-staining. Among the various cultured malignant and nonmalignant human cell lines tested, these mAbs reacted only with leukemic T-cell lines with one exception. Results consistent with the above were obtained from studies in which uncultured malignant cell specimens from different cancer patients were tested against these mAbs; they reacted only with T leukemia cells. Among various uncultured normal cell specimens tested, these mAbs did not react with thymocytes, bone marrow cells, peripheral blood lymphocytes containing B and T cells, purified T cells, monocytes, granulocytes, or erythrocytes. However, they reacted with platelets. It should be noted that mAb SN1 does not react with platelets. SN2 and SN2a immunoprecipitate a Mr = 37,000 antigen from both a ?125?I-labeled leukemia antigen preparation and from ?125?I-labeled glycoproteins of MOLT-4 cells. These mAbs will be useful in diagnosis and perhaps also in therapy of human T-cell leukemia, which is known to be associated with poor prognosis. It is important to note that immunotoxins prepared by conjugating ricin A chain with mAbs SN1 and SN2 showed specific killing of human T leukemia cells in vitro. (2)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA019304-09
Application #
3165123
Study Section
Experimental Immunology Study Section (EI)
Project Start
1976-06-30
Project End
1986-12-31
Budget Start
1985-04-01
Budget End
1986-12-31
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Seon, Ben K; Haba, Akinao; Matsuno, Fumihiko et al. (2011) Endoglin-targeted cancer therapy. Curr Drug Deliv 8:135-43
Matsuno, F; Haruta, Y; Kondo, M et al. (1999) Induction of lasting complete regression of preformed distinct solid tumors by targeting the tumor vasculature using two new anti-endoglin monoclonal antibodies. Clin Cancer Res 5:371-82
Seon, B K; Matsuno, F; Haruta, Y et al. (1997) Long-lasting complete inhibition of human solid tumors in SCID mice by targeting endothelial cells of tumor vasculature with antihuman endoglin immunotoxin. Clin Cancer Res 3:1031-44
Okazaki, M; Luo, Y; Han, T et al. (1993) Three new monoclonal antibodies that define a unique antigen associated with prolymphocytic leukemia/non-Hodgkin's lymphoma and are effectively internalized after binding to the cell surface antigen. Blood 81:84-94
Takeuchi, T; Barcos, M P; Seon, B K (1991) Monoclonal antibody SN10 which shows a highly selective reactivity with human B leukemia-lymphoma and is effectively internalized into cells. Cancer Res 51:2985-93
Luo, Y; Hara, H; Haruta, Y et al. (1989) Establishment of ascitic tumor of human pre-B acute lymphoblastic leukemia in nonconditioned nude mice. Cancer Res 49:706-10
Biddle, W C; Haruta, Y; Seon, B K et al. (1989) In vitro and in vivo cytotoxic activity of anti-human leukemia monoclonal antibodies SN5c and SN6 daunorubicin conjugates. Leuk Res 13:699-707
Hara, H; Luo, Y; Haruta, Y et al. (1988) Efficient transplantation of human non-T-leukemia cells into nude mice and induction of complete regression of the transplanted distinct tumors by ricin A-chain conjugates of monoclonal antibodies SN5 and SN6. Cancer Res 48:4673-80
Matsuzaki, H; Haruta, Y; Fukukawa, T et al. (1987) Unique epitopes of common acute lymphoblastic leukemia antigen detected by new monoclonal antibodies. Cancer Res 47:2160-6
Matsuzaki, H; Seon, B K (1987) Molecular nature of a cell membrane antigen specific for human T-cell acute lymphoblastic leukemia. Cancer Res 47:4283-6

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