Inhibiting CFH May Improve Responses to Rituximab in CLL

Inhibition of complement dependent cytotoxicity (CDC) regulatory proteins may improve responses to rituximab among some patients with chronic lymphocytic leukemia (CLL), according to a study published in PLoS One.¹

Rituximab, which is used to treat B cell–CLL alone or with chemotherapy, is thought to be effective due to CDC induction. Failure to induce CDC is associated with rituximab resistance.

One mechanism associated with lack of CDC induction is the presence of complement factor H (CFH), a soluble protective protein. For this ex vivo study, blood samples were obtained from 11 patients with B cell–CLL to determine whether inhibiting the CDC-protective protein with or without a negative control monoclonal antibody would affect rituximab resistance.

Rituximab-sensitivity was determined for each sample; 10 were classified as “non-responders.”

The researchers found that a CFH-targeted monoclonal antibody conferred cancer cell sensitivity to rituximab. In 1 patient’s sample that remained refractory, combining the CFH-targeted antibody with the negative control was sufficient for inducing CDC, thereby overcoming rituximab resistance.

The authors concluded that these “results suggest that CDC of malignant B-CLL cells can be augmented when rituximab is used with a CFH [monoclonal antibody] specific to tumor cells, even when the cells are rituximab non-responsive.”

A phase 1 trial is being planned.

Reference

1. Winkler MT, Bushey RT, Gottlin EB, et al. Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody. PLoS ONE. 2017;12(6):e0179841.