Effect of obexelimab on the production of anti-RBC Ab and cytokines from patients with warm autoimmune hemolytic anemia Open Access

• Obexelimab reduced the production of anti-RBC Ab by 25% in unstimulated, by 5-10% in PHA-stimulated, and by 35% in PWM-stimulated cultures.

• Obexelimab reduced IL-10 production in PHA-stimulated cultures, and increased IFN-g, IL-2, IL-17, TNF-a, IL-10, and TGF-b in PWM-ones.

Obexelimab is a bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit the activity of B-lineage cells. It is currently being evaluated in humans with various autoimmune diseases, including warm haemolytic anemia (wAIHA). In this study, we evaluated the in vitro effect of obexelimab on the production of anti-red blood cell (RBC) autoantibodies and cytokines in blood samples collected from a cohort of wAIHA patients followed at a single tertiary hematologic center. Obexelimab reduced the production of anti-RBC autoantibodies by 25% in unstimulated, and by 5-10% in PHA-stimulated cultures, both at 15 and 405 mcg/mL; in PWM-stimulated cultures, obexelimab reached an inhibition of 35% at 405 mcg/mL. Obexelimab (15 mcg/mL) reduced IL-10 production in PHA-stimulated cultures from wAIHA patients. Moreover, it induced an increase of IFN-gamma, IL-2, and IL-17 production (approximately 20-30%), and a milder increase of TNF-alpha, IL-10, and TGF-beta (approximately 10%), in PWM-stimulated cultures. Soluble receptor IL-2Ra was slightly reduced and APO-1/FAS was minimally increased in obexelimab (15 mcg/mL) treated PWM-stimulated blood cell cultures. Collectively, these findings support the notion that obexelimab exerts an immunomodulatory effect on RBC-specific autoantibody and cytokine production in wAIHA.