Assessing the Safety of Second-Generation Anti-CTLA4 Variants in Primate Models

Ipilimumab is an antibody that targets CTLA-4, a receptor on certain immune cells. There are new versions of this antibody, BMS-986218 and BMS-986249, which work differently. BMS-986218 is modified to bind more strongly to immune cells and might help fight cancer better by removing some immune cells in the tumor. BMS-986249 is a special type of antibody that is hidden until it gets to a tumor, which might reduce side effects while still working well.

Tests in monkeys showed that all three antibodies activated immune cells, but BMS-986218 did so more than ipilimumab, and BMS-986249 did so less and later. The monkeys tolerated the drugs well at certain doses, but some had mild diarrhea or lost a little weight. Higher doses caused serious problems for some monkeys, and a few had to be put down.

The main side effect was inflammation in tissues, which was worst with BMS-986218 and least with BMS-986249. The stomach, cecum, colon, and kidneys were most affected, but other organs could be affected at higher doses. Most of these effects got better after the treatment stopped, but some monkeys still had problems.

The best doses for the monkeys were 3 mg/kg for BMS-986218, 10 mg/kg for ipilimumab, and 50 mg/kg for BMS-986249. These results suggest that the new antibodies might be better than ipilimumab with more benefits and fewer risks.

This study was presented at a conference and published in a journal by several authors.