We have demonstrated that radiolabeled monoclonal antibodies reactive with the panhematopoietic CD45 antigen can deliver relatively specific irradiation to lymphohematopoietic tissues in preclinical studies in mice and macaques as well as in patients undergoing bone marrow transplantation for acute leukemia. The proposed studies examine strategies for improving the """"""""therapeutic ratio"""""""" of radiation delivered to target lymphohematopoietic tissues, as compared to other normal organs, by 131I-labeled anti- CD45 antibody. These will include study of the effect of the use of an unlabeled preclearing dose"""""""" of antibody prior to administration of radiolabeled antibody, further definition of the relationship between antibody dose and relative lymphohematopoietic radiation, and the use of isotopes (186Re and 188Re) which have half lives which are shorter than that of 131I. Further studies will determine if radiolabeled anti-CD45 antibody can facilitate the engraftment of donor marrow, alone or with supplemental total body irradiation (TBI), by ablating host marrow and producing immunosuppression in mice undergoing marrow transplantation with T cell-depleted marrow from donors matched or mismatched for minor or major histocompatibility antigens. The ability to increase the dose of radiation to lymphohematopoietic tissues while minimizing the exposure of normal organs may decrease the high rate of relapse in patients undergoing marrow transplantation for advanced leukemia. It may also decrease the high rate of rejection of HLA- mismatched or unrelated donor marrow which has been depleted of T cells in an attempt to lower the incidence of Graft-vs.-Host Disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08CA001690-01
Application #
3080116
Study Section
Cancer Institutional Fellowship Review Committee (CT)
Project Start
1992-09-01
Project End
1995-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109