Phase 1/2a Clinical Trials of Bi‐1206, a Monoclonal Antibody to Fcγriib, Administered as a Single Agent or in Combination With Rituximab in Subjects With B‐cell Malignancies

Karlsson, Ingrid; Traub, Stephanie; Järås, Kerstin; Edwards, David I.; Gramming, E.; Andersson, M. Lindell; To, Ye Mong; Mårtensson, Linda; Teige, Ingrid; Dyer, Martin J.S.; Radford, John; Collins, Graham P.; Frendéus, Björn; McAllister, Andres; Davies, Andrew

doi:10.1002/hon.206_2631

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous report by Williams and colleagues (30) concluded that anti-CD32b mAs would have limited therapeutic potential due to normal tissue CD32b expression driving antibody clearance. More recently, however, disclosures describing clinical activity of the Fc WT CD32b-targeted mAb BI-1206 suggests that therapeutically relevant exposures are being achieved in patients (31).…”

Section: Discussionmentioning

confidence: 99%

Development of Anti-CD32b Antibodies with Enhanced Fc Function for the Treatment of B and Plasma Cell Malignancies

Molony

Chen

et al. 2020

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

The sole inhibitory Fcg receptor CD32b (FcgRIIb) is expressed throughout B and plasma cell development and on their malignant counterparts. CD32b expression on malignant B cells is known to provide a mechanism of resistance to rituximab that can be ameliorated with a CD32b-blocking antibody. CD32b, therefore, represents an attractive tumor antigen for targeting with a monoclonal antibody (mAb). To this end, two anti-CD32b mAbs, NVS32b1 and NVS32b2, were developed. Their complementarity-determining regions (CDR) bind the CD32b Fc binding domain with high specificity and affinity while the Fc region is afucosylated to enhance activation of FcgRIIIa on immune effector cells. The NVS32b mAbs selectively target CD32b þ malignant cells and healthy B cells but not myeloid cells. They mediate potent killing of opsonized CD32b þ cells via antibody-dependent cellular cytotoxicity and phagocytosis (ADCC and ADCP) as well as complement-dependent cytotoxicity (CDC). In addition, NVS32b CDRs block the CD32b Fc-binding domain, thereby minimizing CD32b-mediated resistance to therapeutic mAbs including rituximab, obinutuzumab, and daratumumab. NVS32b mAbs demonstrate robust antitumor activity against CD32b þ xenografts in vivo and immunomodulatory activity including recruitment of macrophages to the tumor and enhancement of dendritic cell maturation in response to immune complexes. Finally, the activity of NVS32b mAbs on CD32b þ primary malignant B and plasma cells was confirmed using samples from patients with B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma. The findings indicate the promising potential of NVS32b mAbs as a single agent or in combination with other mAb therapeutics for patients with CD32b þ malignant cells.

show abstract

Section: Discussionmentioning

confidence: 99%