Harnessing MEN1112: A Potent Anti-AML Strategy Targeting Bst1/CD157 with Enhanced CD16 Affinity

Bst1/CD157 is a transmembrane protein that is part of the ADP-ribosyl-cyclase family and is found on certain blood cells like monocytes and neutrophils. It has been shown to be present in nearly all Acute Myeloid Leukemia (AML) cases, either at the time of diagnosis or during a relapse.

A humanized antibody, MEN1112, has been developed to target Bst1/CD157 with high specificity and potency. It was derived from a mouse Fab fragment that was selected for its ability to recognize the Bst1/CD157 protein and was then transformed into a full IgG1 version using a potent cell line. MEN1112 exhibits an exceptionally high binding affinity to Bst1/CD157, with an EC50 of 1nM, as determined by flow cytometry, and no binding to antigen-negative cell lines was observed.

This antibody also has an improved affinity for Fc receptors on effector cells, particularly the CD16A receptor, due to the absence of fucose residues in its Fc domain. The slow internalization of Bst1/CD157 upon binding with MEN1112 is advantageous for the antibody's Antibody Dependent Cell-mediated Cytotoxicity (ADCC) efficacy. Collectively, MEN1112's high affinity for Bst1/CD157, its enhanced interaction with CD16A Fc receptors, and its minimal internalization suggest that it could be a potent agent against AML through ADCC.

The disclosures indicate that several individuals associated with Oxford BioTherapeutics and Menarini Ricerche SpA, as well as Menarini Biotech srl, are employed by these companies.