Photo courtesy of the
University of Southampton
A newly developed monoclonal antibody (mAb) can reverse resistance to other mAbs in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), according to research published in Cancer Cell.
Investigators found that some cancer cells draw mAbs inside themselves, making them invisible to immune cells.
But a mAb called BI-1206 can prevent this process and enhance cancer killing by binding to a molecule called FcγRIIB.
In preclinical experiments, BI-1206 was able to overcome resistance to mAbs such as rituximab.
“With more monoclonal antibody treatments being developed, there is an urgent need to understand how tumors become resistant to them and develop ways to overcome it,” said study author Mark Cragg, PhD, of the University of Southampton in the UK.
“Not only does BI-1206 appear to be able to reverse resistance to a range of monoclonal antibodies, it is also effective at directly killing cancer cells itself.”
In the Cancer Cell paper, BI-1206 is referred to as 6G11. The investigators found that 6G11 can block rituximab internalization and has “potent antitumor activity” in vitro. 6G11 was also well-tolerated and did not prompt cytokine storm.
In a mouse model of CLL, 6G11 enhanced rituximab-mediated depletion of primary CLL cells and improved responses when compared to rituximab alone.
In mice engrafted with cells from patients with CLL that was refractory to rituximab, ofatumumab, and/or alemtuzumab, 6G11 alone depleted CLL cells but did not improve overall response rates compared to rituximab alone. However, 6G11 in combination with rituximab did improve overall response rates compared to rituximab alone.
In a mouse model of MCL, neither 6G11 nor rituximab alone improved long-term survival. However, 30% of mice treated with both drugs survived tumor-free out to 100 days.
Combining 6G11 with obinutuzumab significantly improved splenic tumor cell depletion in mice with CLL. And more than 90% of mice that received 6G11 and alemtuzumab had a complete response to the treatment.
The investigators said these data suggest 6G11 can overcome mAb resistance for multiple targets. They said the drug will be tested in patients with CLL and non-Hodgkin lymphoma in an early stage clinical trial.
