Marrow Ablative and Immunosuppressive Effects of131I-Anti-CD45 Antibody in Congenic and H2-Mismatched Murine Transplant Models

Abstract

Abstract Targeted hematopoietic irradiation delivered by131I-anti-CD45 antibody has 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 immunosuppressive effects of such low dose rate irradiation must be quantitated. We have examined the ability of 131I-anti-CD45 antibody to facilitate engraftment in Ly5-congenic and H2-mismatched murine marrow transplant models. Recipient B6-Ly5a mice were treated with 30F11 antibody labeled with 0.1 to 1.5 mCi 131I and/or total body irradiation (TBI), followed by T-cell–depleted marrow from Ly5b-congenic (C57BL/6) or H2-mismatched (BALB/c) donors. Engraftment was achieved readily in the Ly5-congenic setting, with greater than 80% donor granulocytes and T cells after 0.5 mCi 131I (estimated 17 Gy to marrow) or 8 Gy TBI. A higher TBI dose (14 Gy) was required to achieve engraftment of H2-mismatched marrow, and engraftment occurred in only 3 of 11 mice receiving 1.5 mCi131I delivered by anti-CD45 antibody. Engraftment of H2-mismatched marrow was achieved in 22 of 23 animals receiving 0.75 mCi 131I delivered by anti-CD45 antibody combined with 8 Gy TBI. Thus, targeted radiation delivered via131I-anti-CD45 antibody can enable engraftment of congenic marrow and can partially replace TBI when transplanting T-cell–depleted H2-mismatched marrow.