Stem cell transplantation can be relied upon to salvage some patients with recurrent or resistant leukemia, but many others continue to succumb to resurgent disease. Studies outlined in this application will test a combination of two anti-CD45 monoclonal antibodies (mAb) for its safety, biologic activity and pharmacokinetic properties in patients with relapsed acute leukemia and CD45+ blast cells who are to receive allogeneic stem cell grafts. Dose escalations, from 6.25 to 6400 mu g/kg, will permit identification of a maximum tolerated dose (MTD) as well as the dose that produces discernable biologic effects in patients. The underlying hypothesis of this research is that the mAb combination will have anti-leukemic activity and will enhance engraftment, without the toxicity associated with standard conditioning regimens. Thus, studies are planned to determine the effects of anti-CD45 mAb dose escalations on normal hematopoiesis and lymphopoiesis, leukemic blast cells and myeloid/platelet engraftment times, as compared with historic controls not receiving the antibodies. By the end of this 2-year study, the safety of the anti-CD45 mAb combination will be established, as will its effects on normal and malignant lymphohemopoietic cells in vivo. Because the mAb to be tested rely on host effector mechanisms rather than conjugated toxins or radionuclides, demonstration of significant biologic activity will indicate the potential of these mAb as tem cell transplant-conditioning agents. In fact, depending on the outcome of the studies proposed, they might well be used as the sole conditioning agent in patients who are to receive allogeneic transplants for nonmalignant disease, or gene modified autologous stem cells.
| Kang, Ki Joo; Sinn, Dong Hyun; Park, Sung Hyun et al. (2010) Adenoma incidence after resection of sporadic colorectal cancer with microsatellite instability. J Surg Oncol 101:577-81 |
| Wulf, Gerald G; Luo, Kang-Li; Goodell, Margaret A et al. (2003) Anti-CD45-mediated cytoreduction to facilitate allogeneic stem cell transplantation. Blood 101:2434-9 |
| Brenner, Malcolm K; Wulf, Gerald G; Rill, Donna R et al. (2003) Complement-fixing CD45 monoclonal antibodies to facilitate stem cell transplantation in mouse and man. Ann N Y Acad Sci 996:80-8 |
| Krance, Robert A; Kuehnle, Ingrid; Rill, Donna R et al. (2003) Hematopoietic and immunomodulatory effects of lytic CD45 monoclonal antibodies in patients with hematologic malignancy. Biol Blood Marrow Transplant 9:273-81 |
