JNJ-64457107, a CD40 Agonist, Induces Cell Death in BCL6(hi)IRF4(neg) GCB Subtype of DLBCL

CD40 is a member of the TNF receptor family that is expressed in multiple tumor types and normal cells including antigen presenting cells (APC), endothelium and platelets. CD40-CD40L signaling is one of the pivotal mechanisms essential for robust antigen presentation and adaptive immunity. JNJ-64457107 (JNJ-107) is an anti-CD40 IgG1 agonistic antibody that is currently in a Phase 1 clinical trial (NCT02829099). JNJ-107/ADC-1013 induced significant anti-tumor activity and immunological memory (Mangsbo 2015). It was also reported that a CD40 agonist, SGN-40, induced direct cytotoxicity in diffuse large B cell lymphoma (DLBCL) cell lines (Burlington 2011), and clinical responses have been noted in this indication (Advani 2009). However, not all DLBCL patients and DLBCL cell lines respond to SGN-40. Thus, a patient selection strategy in B cell malignancies may be beneficial. Here, we investigated the mechanism of action and potential biomarkers of response to JNJ-107 in DLBCL.