Abstract
AbstractMultiple myeloma remains an incurable malignancy because of marked resistance of tumor cells to conventional chemotherapeutic agents. Alternative strategies are needed to solve these problems. To develop a new strategy, we have generated a monoclonal antibody (MoAb), which detects a human plasma cell-specific antigen, HM1.24. In this report, we evaluated the in vivo antitumor effect of unconjugated anti-HM1.24 MoAb on human myeloma xenografts implanted into severe combined immunodeficiency (SCID) mice. Two models of disseminated or localized tumors were established in SCID mice by either intravenous or subcutaneous injection of human myeloma cell lines, ARH-77 and RPMI 8226. When mice were treated with a single intraperitoneal injection of anti-HM1.24 MoAb 1 day after tumor inoculation, the development of disseminated myeloma was completely inhibited. In mice bearing advanced tumors, multiple injections of anti-HM1.24 MoAb reduced the tumor size and significantly prolonged survival, including tumor cure, in a dose-dependent manner. The proliferation of cultured human myeloma cells was inhibited in vitro by anti-HM1.24 IgG-mediated complement-dependent cytotoxicity, but not by the antibody alone. Moreover, spleen cells from SCID mice mediated antibody-dependent cell cytotoxicity against RPMI 8226 cells. These results indicate that anti-HM1.24 MoAb can be used for immunotherapy of multiple myeloma and related plasma cell dyscrasias.
Highlights
Multiple myeloma remains an incurable malignancy because of marked resistance of tumor cells to conventional chemotherapeutic agents
Several investigators have reported immunotherapeutic approaches targeting to cell surface antigens on myeloma cells, using anti-CD38 antibody,[6,7,8] anti-CD54 antibody,[9] or soluble CD16.10 because these molecules are expressed on normal tissues including hematopoietic stem cells,[11,12] these approaches may induce side effects related to crossreactivity in vivo
Our results indicate that the HM1.24 antigen serves as a target for immunotherapy of multiple myeloma and related plasma cell dyscrasias
Summary
Multiple myeloma remains an incurable malignancy because of marked resistance of tumor cells to conventional chemotherapeutic agents. Spleen cells from SCID mice mediated antibody-dependent cell cytotoxicity against RPMI 8226 cells These results indicate that anti-HM1.24 MoAb can be used for immunotherapy of multiple myeloma and related plasma cell dyscrasias. Partial remissions of up to 60% are obtained with a variety of chemotherapeutic protocols, the overall survival has not improved over the past three decades.[1] Myeloablative chemotherapy followed by allogeneic or autologous hematopoietic stem cell transplantation has increased the incidence of complete remission,[2,3] but relapses are still observed even after remission Because these chemotherapies have only limited value, alternative strategies are needed to solve these problems. Our results indicate that the HM1.24 antigen serves as a target for immunotherapy of multiple myeloma and related plasma cell dyscrasias
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