CD48 MONOCLONAL-ANTIBODY K31 FOR BONE-MARROW TRANSPLANTATION - T-DEPLETING CAPACITY AND INFLUENCE ON HEMATOPOIETIC PROGENITORS

Allogeneic bone marrow transplantation (BMT) from HLA-identical siblin g donors provides the only chance of cure for a variety of hematologic al diseases, namely relapsed acute leukemias and chronic myeloid leuke mia. Unfortunately, an HLA-matched sibling is available to only one th ird of the patients being eligible for BMT. For this reason, HLA-match ed unrelated bone marrow donors have been increasingly used in the rec ent years. Due to the greater degree of histoincompatibility, acute gr aft-versus-host reaction (GVHR) is a major problem in unrelated BMT, o ccurring in 50-80% of the recipients when pharmacological prophylaxis with cyclosporin A and/or methotrexate is performed (1-4). Thus, more effective GVHR prophylaxis, such as ex-vivo T cell depletion of the gr aft, is required. However, T depletion has some major limitations: Bes ides a higher risk of relapse, the incidence of graft rejection is lar gely increased after transplantation of T-depleted marrow from both HL A-matched siblings and unrelated donors (5-7). In this context, we hav e studied the possibility of preventing graft rejection by reducing th e immunogenicity of the bone marrow (BM) graft. As reported recently, we found that pretreatment with the CD48 monoclonal antibody K31 plus complement (C) strongly reduces the immunogenicity of human BM by depl eting antigen presenting cells (8,9). CD48 is a glycosyl phosphatidyli nositol-anchored p41 molecule which has been cloned (10). Belonging to the immunoglobulin gene superfamily, CD48 has significant sequence ho mology to the adhesion molecules CD2 and LFA-3 (CD58) and may act as a ligand for activated CD2 (11,12). The antigen is expressed on a varie ty of leukocytes, in particular lymphatic and monocytic cells (8,13). Thus, selective elimination of both graft-versus-host and host-versus- graft reaction-mediating cells from BM grafts should be possible by us ing CD48 MoAbs. In the present study, we have investigated the T-deple ting capacity of K31 and its influence on hematopoietic progenitors in order to evaluate its suitability for clinical BM transplantation.