Abstract

We have used monoclonal antibodies against a normal differentiation antigen to treat mouse leukemias. In those studies, treatment of a transplanted T cell leukemia with monoclonal antibody against the Thy 1 differentiation antigen induced prolonged survival and cure in a significant proportion of mice. It also led to a modest but significant prolongation of chemotherapy induced remissions in mice with spontaneous lymphoid malignancies. The purpose of the proposed studies is to evaluate the use of monoclonal anti-Thy 1.1 antibodies for the therapy of transplanted and spontaneous neoplastic disease in mice. The influence of the clearance rates, biodistribution, and avidity of monoclonal antibodies of each immunoglobulin subclass will be determined, as well as their interaction with effector cells. Combinations of antibodies against different T cell determinants will be used in an attempt to prevent the emergence of antigen negative tumor cell variants. The results of these studies should help elucidate the principles governing monoclonal antibody therapy and facilitate optimal design of future clinical trials in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026386-08
Application #
3167290
Study Section
Experimental Immunology Study Section (EI)
Project Start
1979-07-01
Project End
1987-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Appelbaum, F R (1997) Allogeneic hematopoietic stem cell transplantation for acute leukemia. Semin Oncol 24:114-23
Appelbaum, F R (1996) The use of bone marrow and peripheral blood stem cell transplantation in the treatment of cancer. CA Cancer J Clin 46:142-64
van der Jagt, R H; Badger, C C; Appelbaum, F R et al. (1992) Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model. Cancer Res 52:89-94
Schultz, K R; Badger, C C; Dombi, G W et al. (1992) Effect of interleukin-2 on biodistribution of monoclonal antibody in tumor and normal tissues in mice bearing SL-2 thymoma. J Natl Cancer Inst 84:109-13
Badger, C C; Rasey, J; Nourigat, C et al. (1991) WR2721 protection of bone marrow in 131I-labeled antibody therapy. Radiat Res 128:320-4
Badger, C C; Davis, J; Nourigat, C et al. (1991) Biodistribution and dosimetry following infusion of antibodies labeled with large amounts of 131I. Cancer Res 51:5921-8
Ali, S A; Warren, S D; Richter, K Y et al. (1990) Improving the tumor retention of radioiodinated antibody: aryl carbohydrate adducts. Cancer Res 50:783s-788s
Bianco, J A; Appelbaum, F R (1990) Biotherapy after marrow transplantation and the use of hematopoietic growth factors. Curr Opin Oncol 2:289-96
Ali, S A; Eary, J F; Warren, S D et al. (1988) Synthesis and radioiodination of tyramine cellobiose for labeling monoclonal antibodies. Int J Rad Appl Instrum B 15:557-61
Anasetti, C; Martin, P J; Morishita, Y et al. (1987) Human large granular lymphocytes express high affinity receptors for murine monoclonal antibodies of the IgG3 subclass. J Immunol 138:2979-81

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