K31 is a promising murine anti-CD48 monoclonal antibody (MAB) which can deplete tissue grafts of antigen presenting accessory cells to reduce their immunogenicity. Because any in vivo use of this MAB will be limited by the human anti-mouse antibody (HAMA) response the overall goal is to use PCR technology to humanize K31. In phase I we will clone and sequence heavy and light chain variable regions of K31, then utilize murine heavy and light chain CDRs to reshape K31 into a human IgG1 monoclonal antibody (hK31). During phase II we will express hK31 using an amplifiable high level antibody expression system developed in this laboratory and test activity of hK31 for in vitro binding and functional activity. At the completion of phase II we plan to initiate preclinical development of hK31. K31 has promise as a therapeutic antibody to improve the transplantation of allo-mismatched T-depleted bone marrow (BM). In vitro data suggests that simultaneous depletion of T cells and accessory cells with K31 reduces the immunogenicity of HLA-mismatched BM grafts which reduces graft rejection. Thus, in contrast to CAMPATH-1 being developed by Burrough Wellcome, K31 may be a useful reagent for preventing both graft-versus-host and host-versus-graft reactions in the situation of HLA-mismatched BM transplantation. While humanization of K31 will not be required for in vitro use, any in vivo use will require a humanized form of K31 (hK31). hK31 has promise to reduce the accessory cell mediated immunogenicity of transplanted solid organs. hK31 associated immunosuppression may be a useful approach for refractory solid organ rejection episodes or recalcitrant autoimmune diseases such as rheumatoid arthritis. hK31 may also be useful for treatment of various lymphomas or leukemias.
