Targeting Multiple Myeloma with AMG 424: A Humanized Bispecific Anti-CD3/CD38 Antibody Approach

Multiple myeloma (MM) is a common blood cancer with a high patient count, and despite advancements, there's an ongoing need for treatments that can address relapses. The focus is on therapies that can eradicate minimal residual disease (MRD). A new approach involves bispecific T cell engager (BiTE) molecules, which can activate T cells to attack cancer cells. CD38, a protein on immune cells, is overexpressed in MM and thus a target for therapy.

AMG 424, a humanized bispecific antibody, is being introduced. It's designed to bind to both T cells and CD38 on MM cells, and it has been engineered to have a unique Fc domain that can interact with nonhuman primate immune cells. The selection of AMG 424 was based on its binding properties to CD3 and CD38, intended to overcome issues related to these interactions.

In vitro tests were conducted on eight new bispecific molecules with varying affinities for CD3 and CD38. These tests included assessing the ability to kill cancer cells, B cell depletion, cytokine release, and the impact of soluble CD38. AMG 424 was chosen for further in vivo studies in mice with human T cells, where it showed significant tumor growth inhibition and survival extension. It also demonstrated efficacy in depleting CD38-expressing cells in nonhuman primates.

Combining AMG 424 with standard treatments showed little impact on its activity. The results suggest that AMG 424 could be a promising therapy for MM, either alone or in combination with existing treatments. The disclosures indicate that several authors are affiliated with Amgen Inc., Xencor, Inc., and Henn Research (Munich) GmbH.