Development of anti-human CADM1 monoclonal antibodies as a potential therapy for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a highly invasive and refractory T-cell malignancy, with poor prognosis. We previously identified that cell adhesion molecule 1 (CADM1) is overexpressed consistently in ATLL cells, and that CADM1 expression increases the adhesion capacity of ATLL cells to endothelial cells and promotes the organ invasion of ATLL cells in a xenograft mouse model. In this study, we first show that newly developed several anti-human CADM1 antibodies, which were complete human IgG antibodies generated by phage display method, specifically recognize CADM1 on ATLL cells. Although most of the CADM1 antibodies did not have a direct cytotoxic effect against CADM1-positive ATLL cells, clone 089-084 exhibited weak but significant antibody-dependent cell-mediated cytotoxic activity. Moreover, clone 103-189 effectively inhibits the interaction between endothelial cells and CADM1-positive ATLL cells. Furthermore, in mice bearing intra-splenic transplantation of EL4 mouse lymphoma cells expressing CADM1, the treatment of 103-189 significantly suppressed the organ invasion of CADM1-positive EL4 cells, resulting in improved survival time of mice. Therefore, since the anti-CADM1 antibody may be useful for the suppression of organ invasion in ATLL patients, combination use of the anti-CADM1 antibody with chemotherapy drugs could be beneficial for the efficient elimination of ATLL cells.