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Blood, Vol. 93 No. 2 (January 15), 1999:
pp. 737-745
Marrow Ablative and Immunosuppressive Effects of
131I-Anti-CD45 Antibody in Congenic and H2-Mismatched
Murine Transplant Models
Dana C. Matthews,
Paul J. Martin,
Cynthia Nourigat,
Frederick R. Appelbaum,
Darrell R. Fisher, and
Irwin D. Bernstein
From the Division of Clinical Research, Fred Hutchinson Cancer
Research Center, Seattle, WA; the Departments of Pediatrics
and Medicine, University of Washington, Seattle, WA; and the
Pacific Northwest National Laboratory, Richland, WA.
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-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 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.
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