On November 3, 2023 AbCellera (Nasdaq: ABCL) reported new data on its T-cell engager (TCE) programs in two poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting (Press release, AbCellera, NOV 3, 2023, View Source [SID1234636932]). The data illustrate how AbCellera is leveraging its TCE platform to discover and develop immuno-oncology therapeutics for multiple tumor targets.
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In its first poster, AbCellera presented data demonstrating that TCE function is determined by multiple factors, including—but not limited to—CD3-binding affinity. Based on these findings, AbCellera developed a high-throughput process that prioritizes TCE function to streamline the selection of diverse CD3-binding antibodies for different tumor targets. AbCellera is currently leveraging its integrated platform to discover and develop TCEs for multiple programs. The poster included data from two of these programs targeting prostate-specific membrane antigen (PSMA) and melanoma-associated antigen 4 (MAGE-A4).
"Altering the affinity of either a small set of CD3-binding antibodies, or an antibody such as SP34-2, is a frequently used strategy to reduce risk of cytokine release syndrome by TCEs. However, we have demonstrated that CD3 affinity alone is not sufficient to optimize TCE function," said Bo Barnhart, Ph.D., VP of Translational Research at AbCellera. "By pairing functionally diverse CD3-binders with a wide range of tumor-binding arms, our TCE platform has identified promising bispecific molecules."
In its second poster, AbCellera presented additional data on its MAGE-A4 x CD3 program, which targets MAGE-A4, a challenging peptide-MHC target. AbCellera used its bispecific platform, OrthoMabTM, to engineer more than 200 bispecific TCEs. Results from high-throughput assessment of these molecules demonstrate that the platform can generate high-quality TCEs for further development.
"Since launching our TCE platform in 2021, we’ve gained a deeper understanding of TCE biology that we believe will enable us to rapidly bring best-in-class molecules to the clinic," said Neil Aubuchon, Chief Commercial Officer at AbCellera. "We look forward to applying these lessons to targets as we work towards bringing better cancer treatments to patients faster."
AbCellera’s poster presentations are available for download here.
About T-Cell Engagers
CD3 T-cell engagers are bispecific antibodies that guide the immune system to find and eliminate cancer cells by binding both cancer-killing T cells and tumor targets at the same time. Developing effective T-cell engagers requires two parental antibodies—a CD3-binding arm that fine-tunes T-cell activation and a tumor-binding arm with high specificity for cancer cells. The small number of available CD3-binding antibodies that can effectively fine-tune T-cell responses has been a barrier to T-cell engager development. To address this barrier, AbCellera developed a complete T-cell engager platform that includes fully human, developable CD3-binding antibodies with unique binding and functional properties. By combining these antibodies with OrthoMabTM, its clinically validated multispecific engineering platform, and its antibody discovery and development engine, AbCellera’s T-cell engager platform is designed to bring new cancer medicines to the clinic faster.