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.
|Matthews, D C; Martin, P J; Nourigat, C et al. (1999) Marrow ablative and immunosuppressive effects of 131I-anti-CD45 antibody in congenic and H2-mismatched murine transplant models. Blood 93:737-45|