| abstract |
CD38 is also expressed in a variety of malignant hematologic diseases, including multiple myeloma. In the present invention, the inventors have generated novel antibodies to CD38 that may be suitable for producing CAR-T cells as well as bispecific antibodies. In particular, we report the development of Bi38-3, a novel bispecific T cell engager that targets CD38 in MM cells and recruited cytotoxic T cells via CD3ε. Bi38-3 lacked the Fc region of the native mAb, contributing to the resistance process, but initiated T cells to proliferate, release cytokines and lyse CD38 positive MM cells in vitro. Similarly, Bi38-3 induced autologous T cells to abolish tumor plasma cells isolated from MM patients both at diagnosis and at relapse. The cytotoxicity initiated by Bi38-3 was limited to cells expressing high levels of CD38 and preserved the integrity of T, B and NK lymphocytes in vitro. Importantly, Bi38-3 rapidly reduced tumor cells in the MM1.S xenograft mouse model of human MM. Together, the results show that the antibody of the present invention is an effective reagent for specifically removing CD38-positive malignant cells without significantly affecting cells expressing low CD38, and has been shown to be effective in the treatment of malignant hematologic diseases, and in particular multiple myeloma. demonstrate that it represents a promising novel immunotherapeutic tool for |