Targeting CD37 with AGS67E: A Promising Therapeutic Approach for Hematological Malignancies

A new antibody drug conjugate, AGS67E, has been created to target CD37, a protein commonly found on cancerous B cells. It is designed to be a treatment for non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and acute myeloid leukemia. AGS67E is composed of a human monoclonal antibody linked to a microtubule-disrupting agent, MMAE, through a cleavable linker.

The drug has shown strong binding, internalization, and cytotoxicity in various models and patient samples of the aforementioned cancers, including stem cells. It has also induced significant anti-tumor effects, with complete tumor regressions observed in xenograft models, even in cases where other treatments have failed.

Flow cytometry and immunohistochemistry assays were developed to confirm AGS67E's binding to normal and patient-derived samples. The drug has a high affinity for B cells and binds less to other types of cells like monocytes, T cells, and neutrophils. It also binds to cynomolgus monkey B cells and is cytotoxic to them as well as human B cells. AGS67E's binding in normal tissues is limited to areas with lymphoid structures.

The drug was found to bind to a significant percentage of NHL and all CLL and AML samples, indicating its potential as a therapeutic agent. This research also marks the first time that CD37's expression in AML has been highlighted as a possible target for treatment.

The study was presented at the 105th Annual Meeting of the American Association for Cancer Research, and the findings suggest AGS67E's potential as a new treatment for these types of leukemia and lymphoma.