Marrow ablative and immunosuppressive effects of I-131-anti-CD45 antibody in congenic and H2-mismatched murine transplant models

Targeted hematopoietic irradiation delivered by I-131-anti-CD45 antibody ha s been combined with conventional marrow transplant preparative regimens in an effort to decrease relapse. Before increasing the proportion of therapy delivered by radiolabeled antibody, the myeloablative and immunosuppressiv e effects of such low dose rate irradiation must be quantitated. We have ex amined the ability of I-131-anti-CD45 antibody to facilitate engraftment in Ly5-congenic and H2-mismatched murine marrow transplant models. Recipient B6-Ly5(a) mice were treated with 30F11 antibody labeled with 0.1 to 1.5 mCi I-131 and/or total body irradiation (TBI), followed by T-cell-depleted mar row from Ly5(b)-congenic (C57BL/6) or H2-mismatched (BALB/c) donors. Engraf tment was achieved readily in the Ly5-congenic setting, with greater than 8 0% donor granulocytes and T cells after 0.5 mCi I-131 (estimated 17 Gy to m arrow) or 8 Gy TBI. A higher TBI dose (14 Gy) was required to achieve engra ftment of HS-mismatched marrow, and engraftment occurred in only 3 of 11 mi ce receiving 1.5 mCi I-131 delivered by anti-CD45 antibody. Engraftment of H2-mismatched marrow was achieved in 22 of 23 animals receiving 0.75 mCi I- 131 delivered by anti-CD45 antibody combined with 8 Gy TBI. Thus, targeted radiation delivered via I-131-anti-CD45 antibody can enable engraftment of congenic marrow and can partially replace TBI when transplanting T-cell-dep leted H2-mismatched marrow. (C) 1999 by The American Society of Hematology.