CD38-Targeted ARMs: Harnessing Universal Antibody Binding for Cancer Immunotherapy

Antibody recruiting molecules (ARMs) are a novel approach in cancer immunotherapy, consisting of bifunctional molecules with a target-binding end and a universal antibody binding terminus (uABT) that can attract IgG antibodies regardless of their antigen specificity. This innovative strategy enhances the immune system's ability to target and destroy cancer cells.

Kleo Pharmaceuticals has created CD38-ARM compounds that target the CD38 protein, which is highly expressed in multiple myeloma cells. These compounds have shown therapeutic effects in three different in vivo models, notably without depleting immune effector cells that also express CD38, unlike existing treatments like Daratumumab.

The efficacy of CD38-ARM was tested in SCID mice with Daudi cell xenografts, nude mice with MOLP-8 cell xenografts, and humanized mice with IL-15 transgenic NOG mice reconstituted with human NK cells. The results showed significant tumor growth inhibition and NK cell activation without depletion, suggesting that the CD38-ARM compounds could be a promising therapeutic option.

In conclusion, the CD38-ARM compounds have demonstrated therapeutic activity across various models, indicating their potential as standalone treatments or as a platform for developing targeted compounds. The findings also suggest that these molecules can engage multiple effector mechanisms for tumor clearance and growth delay, offering a broad therapeutic scope.

Disclosures indicate that several individuals are affiliated with Kleo Pharmaceuticals, holding employment and/or equity ownership positions within the company.