Propel optimal T-cell engagers to IND with a fully integrated discovery and development engine
Immunotherapies are transforming cancer treatment by mobilizing the immune system to combat cancer. Bispecific CD3 T-cell engagers — a type of immunotherapy — guide the immune system to find and eliminate cancer cells by binding both cancer-killing T cells and tumor targets at the same time.
Bispecific T-cell engagers are made up of two parental antibodies — a CD3-binding arm that fine-tunes T cell activation and a tumor-binding arm with high specificity for cancer cells. But finding parental antibodies that function optimally as a pair has been challenging.
At AACR 2023, we presented two posters that demonstrate how we’re breaking barriers to address both sides of this challenge.
Identifying bispecific T-cell engagers with optimal potency and cytokine release profiles with differentiated CD3-binding antibodies
We presented a comprehensive data package on our novel, fully human CD3-binding antibodies, including binding and functional comparisons to molecules commonly used for T-cell engager development. Proof-of-concept data illustrated how these antibodies could enable the development of optimal T-cell engagers for different tumor targets.
Breaking barriers to access intracellular targets with T-cell engagers: Discovery of diverse, developable, and ultra-specific antibodies against a MAGE-A4 pMHC
Our second poster described the discovery of highly specific and developable antibodies against a validated peptide-major histocompatibility complex (pMHC) tumor target called MAGE-A4-pMHC.
T-cell engager targets have generally been limited to proteins located on the surface of cancer cells. Access to intracellular proteins that are expressed inside cancer cells would expand the target pool. Peptides of these intracellular proteins presented on MHC class I provide opportunities for T-cell engager development.
We used our integrated antibody discovery, characterization, and engineering technologies to discover a panel of fully human MAGE-A4-pMHC-binding antibodies that are diverse, ultra-specific, and developable. Strategic selection and pairing of our target- and CD3-binding antibodies has the potential to power the discovery of optimal T-cell engagers targeting MAGE-A4-pMHC.