Antibodies specific for cd38 and uses thereof

Abstract

CD38 is also expressed in a variety of hematological malignancies, including multiple myeloma. In the present invention, the inventors have obtained a novel antibody against CD38, which can be suitable for the production of bispecific antibodies as well as CAR-T cell populations. In particular, the inventors report the development of Bi38-3, which is a novel bispecific T cell binding agent that targets CD38 on MM cells and establishes cytotoxic T cells through CD3 epsilon. The Bi38-3 lacks the Fc region of the natural mAb, while the Fc region contributes to the resistance process, but elicits T cell proliferation, release of cytokines and lysis of CD38 positive MM cells in vitro. Similarly, Bi38-3 induces autologous T cells to eliminate tumor plasma cells isolated from MM patients at the time of diagnosis and recurrence. The cytotoxicity caused by Bi38-3 is only limited to cells expressing high-level CD38, and the integrity of T, B and NK lymphocytes is maintained in vitro. More importantly, the Bi38-3 can be used for rapidly reducing tumor cells in an MM1. S xenotransplantation mouse model of human MM. In conclusion, the result shows that the antibody is an effective reagent for specifically removing CD38 positive malignant cells, does not obviously influence CD38 low-expression cells, and is a novel immunotherapy tool expected to treat hematological malignancies, especially multiple myeloma.

Description

technical field [0001] The present invention belongs to the field of medicine, in particular to the field of oncology. Background technique [0002] CD38 is a type II transmembrane glycoprotein. Functions of CD38 include receptor mediation in adhesion and signaling events as well as enzymatic activity. CD38 is normally found in hematopoietic cells and solid tissues. For hematopoietic cells, most medullary thymocytes are CD38 + , resting and circulating T cells and B cells are CD38-, activated cells are CD38 + . CD38 is also expressed on approximately 80% of resting NK cells and monocytes, as well as lymph node germinal center lymphoblastoid cells, plasma B cells and some intrafollicular cells. CD38 can also be expressed by dendritic cells. A large proportion of normal myeloid cells, especially precursor cells, express CD38. Furthermore, 50-80% of cord blood cells are CD38+ and remain in human blood for the first two to three years of life. In addition to lymphoid pre...

AI Technical Summary

Problems solved by technology

However, after proteasome inhibitors (PIs), immunomodulators (IMIDs) and mAbs, the overall survival rate of patients with relapsed disease remains extremely low and MM remains an incurable disease

Images