Acute Myeloid Leukemia (AML) is one of the most common acute leukemia in adults and still with a large unmet need for new therapies. The 5-year overall survival (OS) rate of AML is ~30%, and standard treatment regimens have changed remarkably little since the 1970s. In particular, antibody drug conjugates (ADCs) have fallen short of expectations in this disease. Despite dozens of new ADCs against various antigens entering clinical trials, still only one ADC (Mylotarg) has received FDA and EMEA approval.

In a translational and multi-country collaboration, VAR2 Pharma, VarCT Diagnostics and University of Copenhagen report that oncofetal chondroitin sulfate (ofCS) is a novel and promising therapeutic target in AML for antibody-based therapies. In this study, we show that ofCS is abundantly present on bone marrow cells from patients with AML, but not on the cells from healthy individuals. Targeting ofCS with one of our Vartumabs – our anti-ofCS antibodies – results in efficient internalization and selective killing of bone marrow cells from patients with AML. Finally, we show that anti-ofCS ADC using an MMAE payload could prolong the survival of mice xenografted transplanted with human AML cells by up to 77 days.

We thank the patients who donated bone marrow and blood samples for this study, the various funding agencies and multiple collaborators without whom this work would not have been possible.

Read more about it here: https://doi.org/10.1182/blood.2024028147