On November 10, 2022 AbCellera (Nasdaq: ABCL) reported the release of new data on its T-cell engager (TCE) platform at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, to be held virtually and at the Boston Convention & Exhibition Center from November 8 to 12, 2022 (Press release, AbCellera, NOV 10, 2022, View Source [SID1234623773]). AbCellera’s poster presentation describes the expansion, further characterization, and validation of a diverse panel of CD3-binding antibodies that can be used to develop T-cell engagers for cancer treatments.

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"The robust data package we are presenting at SITC (Free SITC Whitepaper) demonstrates that our panel includes antibodies that are distinct from molecules commonly used for CD3 T-cell engager development," said Bo Barnhart, Ph.D., VP, Translational Research at AbCellera. "By combining this panel with the OrthoMab bispecifics platform and high-throughput antibody analytics, we have shown that we can rapidly identify developable T-cell engagers that balance potent cytotoxicity and low cytokine release."

CD3 T-cell engagers are bispecific antibodies that redirect T cells to kill tumor cells. 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. Pairs of parental antibodies that work well together are rare, creating a need for diverse panels of developable antibodies that can be combined and tested at scale to find optimal clinical candidates.

To address the paucity of anti-CD3 antibodies for TCEs, AbCellera used its integrated antibody discovery, characterization, and engineering technologies to discover and validate an extensive panel of fully human CD3-binding antibodies. New data presented at SITC (Free SITC Whitepaper) includes epitope binning analysis, revealing antibodies with species cross-reactivity that bind epitopes distinct from commonly used parental antibodies, such as SP34-2. AbCellera also conducted a second discovery campaign strategically designed to enhance the number of cross-reactive antibodies in the panel, resulting in hundreds of additional unique antibody sequences to be characterized.

Developing bispecific antibodies that potently eliminate cancer cells without inducing toxicity has been a significant challenge limiting T-cell engager development. In a proof-of-concept study, AbCellera used its OrthoMabTM bispecifics platform to create CD3 x EGFR T-cell engagers. High-throughput functional and biophysical assays identified potent tumor-cell killing T-cell engager molecules that maintained low levels of cytokine production without the need for further engineering or optimization.

"We debuted our T-cell engager platform at the AACR (Free AACR Whitepaper) annual meeting in April of this year, and in less than six months, we have greatly expanded the data package supporting this platform," said Murray McCutcheon, Ph.D., Senior VP, Corporate Development at AbCellera. "The remarkable progress demonstrates the speed of AbCellera’s antibody discovery engine, the quality of the antibodies in our T-cell engager panel, and the potential impact it has for partners looking to accelerate development of new cancer treatments."