Marrow ablative and immunosuppressive effects of 131I-anti-CD45 antibody in congenic and H2-mismatched murine transplant models.
Targeted hematopoietic irradiation delivered by 131I-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-Ly5(a) 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 Ly5(b)-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 mCi 131I 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 via 131I-anti-CD45 antibody can enable engraftment of congenic marrow and can partially replace TBI when transplanting T-cell-depleted H2-mismatched marrow.
Matthews
D C
DC
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. dmatthew@fhcrc.org
Martin
P J
PJ
Nourigat
C
C
Appelbaum
F R
FR
Fisher
D R
DR
Bernstein
I D
ID
D000042:Absorption; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D006085:Graft Survival; D006183:H-2 Antigens / Q000032:analysis / Q000276:immunology; D007165:Immunosuppression Therapy; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008297:Male; D051379:Mice; D051381:Rats; D013601:T-Lymphocytes; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D007457:Iodine Radioisotopes; D017493:Leukocyte Common Antigens