On April 8, 2022 AbCellera (Nasdaq: ABCL), a technology company focused on next-generation antibody discovery, reported the release of data on its new T cell engager platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting (Press release, AbCellera, APR 8, 2022, View Source [SID1234611759]). AbCellera’s poster presentation describes the discovery, characterization, and validation of a diverse panel of CD3-binding antibodies that can be used to develop bispecific CD3 T cell engagers for new cancer treatments.

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"T cell engagers are widely recognized for their tremendous potential as precision oncology therapeutics. However, a limited pool of available CD3-binding antibodies and technological challenges in engineering bispecifics have hindered development, leading to many first-generation molecules with poor efficacy or safety," said Bo Barnhart, Ph.D., VP, Translational Research at AbCellera. "Our discovery engine has allowed us to build a panel of hundreds of diverse and fully human CD3-binding antibodies. Combined with our OrthoMabTM bispecific platform, this enables rapid screening of many combinations of CD3- and tumor antigen-binding antibodies to find pairs with optimal biological function and good developability."

CD3 T cell engagers, which bind to T cells and cancer cells simultaneously, are able to redirect T cells to tumor cells, regardless of T cell specificity. Two different parental antibodies, a CD3-targeting antibody that fine-tunes T cell activation and a tumor-targeting antibody with high specificity for cancer cells, are needed to create an optimal bispecific T cell engager. Highly diverse panels of developable and functionally validated parental antibodies increase the probability of finding effective and manufacturable CD3 T cell engagers and reduce the need for downstream engineering to eliminate liabilities.

AbCellera used its technology stack to discover a panel of CD3-binding antibodies from humanized mice. Bioinformatic analysis revealed high sequence diversity, including somatic hypermutation, a range of CDR3 lengths, and diverse V gene usage. The panel was also found to be functionally diverse, including a broad range of CD3 affinities and T cell activation potencies. Biophysical characterization demonstrated that AbCellera’s CD3-binding antibodies have favorable developability properties, which may reduce the time and technical risks of downstream protein engineering, including low mean hydrophobicity, self-association, and polyspecificity.

AbCellera used its clinically validated bispecifics platform, OrthoMabTM, to pair the CD3-binding antibodies with a single EGFR-binding arm to validate the panel in bispecific formats. The resulting bispecific antibodies activated T cells with a range of potencies and led to T cell-mediated tumor cell killing of EGFR-expressing cell lines.

"The data from our T cell engager program, which we initiated in late 2021, show the power and speed of AbCellera’s robust platform," said Neil Berkley, AbCellera’s Chief Business Officer. "Our panel of CD3-binding antibodies offers partners the ability to unlock this promising modality and accelerate their oncology programs by streamlining the development of new cancer treatments."

Details on AbCellera’s presentation at AACR (Free AACR Whitepaper) are as follows:

Title: Redirecting T cells to tumor targets with functionally diverse CD3-binding antibodies
Presenter: Bryan (Bo) C. Barnhart, Ph.D., VP Translational Research, AbCellera
Session: Antibodies and Immune Therapies — Abstract #312
Date and time: Sunday, April 10 at 1:30-5:00 PM CDT

The poster is available for viewing here.