The primary objective is to utilize our generated anti-human leukemia monoclonal antibodies (McAbs) to develop new therapeutic means (e.g., idiotype vaccines), to study immunological, biological and biochemical properties of the leukemia antigens, to find new clues as to the pathogenesis of human leukemia, and to effectively use in the diagnosis and in the monitoring of leukemia patients. In the generation of the anti-leukemia McAbs, we are expanding our earlier success in generating anti-T leukemia McAbs into generating anti-non-T leukemia McAbs. Thus, anti-leukemia McAbs are being generated by a very efficient and unconventional approach. In this approach, immunologically-active human leukemia associated cell membrane antigens are isolated from large quantities (e.g., 5 X 1010 cells) of human leukemia cells of different phenotypes (i.e., T, pre-B and non-T/non-B) by use of a novel purification system. The isolated antigens are being successfully utilized to generate anti-leukemia McAbs. Through this unconventional approach to generating anti-leukemia McAbs, we have generated many (over 20) McAbs directed toward several different leukemia-associated cell surface antigens. Some of these McAbs show strikingly high specificity for leukemia cells and define unique leukemia antigens. These high specificity McAbs and some of new high specificity McAbs generated during the early stages of the proposed grant period will be utilized to achieve the objectives described above. We wish to test the validity and limit of the widely accepted hypothesis that individual types of human leukemias represent a frozen state (""""""""maturation arrest"""""""") of clonal cells at different stages of normal hematopoietic cell differentiation. Our two unique T cell leukemia antigens TALLA (T acute lymphoblastic leukemia antigen) and GP37 defined by McAbs SN1 and SN2, respectively, present to us unique opportunities to test this hypothesis because our evidence strongly indicates that these antigens are not normal differentiation antigens. Furthermore, our recently discovered novel non-T leukemia associated antigen, termed GP160, appears to provide us with an important opportunity to investigate the target cells for leukemogenesis as well as to test that """"""""maturation arrest"""""""" hypothesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA019304-10A1
Application #
3165120
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1976-06-30
Project End
1989-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
10
Fiscal Year
1987
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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