On April 17, 2023 AbCellera (Nasdaq: ABCL) reported new data on its T-cell engager (TCE) platform in two poster presentations at the American Society for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, which is being held at the Orange County Convention Center in Orlando, Florida, from April 14 to 19, 2023 (Press release, AbCellera, APR 17, 2023, View Source [SID1234630214]). AbCellera debuted its TCE platform at AACR (Free AACR Whitepaper) 2022 with data describing the diversity of its CD3-binding antibodies. Presentations at AACR (Free AACR Whitepaper) 2023 illustrated how AbCellera streamlines the development of TCEs with optimal functional properties for diverse tumor targets.

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"T-cell engagers are amongst the most promising new modalities in cancer therapy. The robust characterization of our novel CD3-binding antibodies in both mono- and bispecific formats illustrates that we can engineer optimal TCEs by fine-tuning tumor cell killing and cytokine release," says Bo Barnhart, Ph.D., VP, Translational Research at AbCellera. "Combined with our ability to discover antibodies against some of the most challenging cancer targets, our engine can enable the development of custom-built TCEs for a wide range of cancers."

First, AbCellera demonstrated that its panel of novel, fully human CD3-binding antibodies can build optimized TCEs that have functional profiles superior to benchmark molecules. The presentation included:

A comprehensive data package on a panel of CD3-binding antibodies, including binding and functional comparisons to molecules commonly used for TCE development.
Two proof-of-concept studies in which novel CD3-binding antibodies were used to engineer TCEs for different tumor targets. The resulting TCEs included bispecific antibodies with high potencies and low cytokine release in in vitro assays. Differences in T-cell function across tumor targets emphasized the importance of selecting the right CD3- and tumor-binding antibodies for an optimal TCE. These data demonstrate how AbCellera’s novel CD3-binding antibodies enable development of custom-built TCEs for different tumor targets.
In another poster, AbCellera described the discovery of highly specific and developable antibodies against a validated peptide-major histocompatibility complex (pMHC) tumor target. Melanoma-associated antigen 4 (MAGE-A4) is a tumor-specific antigen expressed by many solid tumors, but not by most healthy tissue. Effectively targeting pMHCs presenting tumor-specific antigens with TCEs could unlock tumor targets that are expressed inside the cell, which are generally inaccessible with this modality. AbCellera used its antibody discovery and development engine to generate antibodies that bind to MAGE-A4-pMHC. Strategic selection and pairing of AbCellera’s target- and CD3-binding antibodies has the potential to power the discovery of optimal TCEs targeting MAGE-A4-pMHC.

"In late 2021, we recognized a gap that was preventing powerful TCE cancer treatments from making it to patients and felt confident that our antibody discovery and development engine could provide the solution," said Murray McCutcheon, Ph.D., Senior VP, Partnering. "In 18 months, we have developed a TCE discovery platform and are leveraging the extensive datasets we’ve generated to custom-build TCEs and help bring better cancer treatments to patients faster."

AbCellera’s poster presentations are available for viewing 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 breaking the barriers of conventional discovery to bring new cancer medicines to the clinic faster.