Marrow Ablative and Immunosuppressive Effects of I-131-anti-CD45 Antibody in Congenic and H2-Mismatched Murine Transplant Models
- Fred Hutchinson Cancer Research Center
- Fred Hutchinson Cancer Center
- Unknown
- BATTELLE (PACIFIC NW LAB)
Targeted hematopoietic irradiation delivered by I-131-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 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 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 I-131 (estimated 17 Gy to marrow) or 8 Gy TBI. A higher TBI dose (14 Gy) was required to achieve engraftment of H2-mismatched mar row, and engraftment occurred in only 3 of 11 mice 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-depleted H2-mismatched marrow.
- Research Organization:
- Pacific Northwest National Lab., Richland, WA (US)
- Sponsoring Organization:
- US Department of Energy (US)
- DOE Contract Number:
- AC06-76RL01830
- OSTI ID:
- 15001482
- Report Number(s):
- PNNL-SA-31615; 820201000; TRN: US200404%%197
- Journal Information:
- Blood, Vol. 93, Issue 2; Other Information: PBD: 1 Dec 1998
- Country of Publication:
- United States
- Language:
- English
Similar Records
Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the alpha-Emitting Radionuclides Bismuth-213 or Astatine-211
Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts