Bispecific antibodies have been shown to have several distinct advantages over monoclonal antibodies. However, testing their effectiveness and safety in vivo has proven to be a specific challenge for this promising therapeutic class.
In a recent poster, researchers at JAX evaluated the CRS-related safety profile in addition to the efficacy of BCMAxCD3 bispecific antibodies. They observed that when NSG™ mice, engrafted with human PBMCs for six days before the antibody treatment, there was a dose-dependent cytokine release. BCMAxCD3 treatment was further tested in 8 different donors and exhibited donor-dependent cytokine release.
To further examine the in vivo cytokine release following antibody interaction with tumor cells, the authors used BCMA-expressing NCI-H929, and Raji-Luc cells in PBMC humanized mice. They observed donor variability in cytokine release with a single antibody treatment, as well as in combination with other drugs, with some donors more sensitive than others.
Taken together, the data suggest that the antibody treatment may have increased the cytokine release activity at high doses. Furthermore, the data seems to support using the JAX humanized mouse platform to evaluate potential immunotoxicity and efficacy of novel bispecific antibodies.