AbCellera Presents Data on T-Cell Engagers Against Four Tumor Targets at AACR 2024
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Insights
AbCellera's recent findings on T-cell engagers (TCEs) suggest a potential breakthrough in cancer therapy. TCEs are designed to direct the body's immune cells to attack tumor cells, a method that holds promise but has faced challenges in balancing efficacy with safety. The data presented indicates that AbCellera has developed TCEs that effectively target tumor cells while minimizing cytokine release, which can cause harmful side effects. This balance could lead to treatments that are both potent and safer for patients.
From a medical research perspective, the specificity of TCEs for solid tumor targets like PSMA, B7-H4 and 5T4 and the avoidance of superagonist activity in their CD28-binding antibodies, are notable. Superagonist activity has been a concern due to its association with toxicity, so this advancement could make TCEs a more viable option for cancer treatment. Moreover, the ability to target intracellular peptides such as MAGE-A4-pMHC could significantly widen the range of addressable cancers, as many tumors express unique peptides that are not accessible with current therapies.
AbCellera's announcement at the AACR Annual Meeting could have considerable implications for the biotech industry and investors. The company's progress in T-cell engager technology may position it favorably in the competitive landscape of cancer immunotherapy. AbCellera's approach to enhancing the therapeutic window and potency of TCEs, while broadening the target space, addresses key limitations that have hindered the widespread adoption of TCEs in solid tumors.
Investors should note that the success of these preclinical developments can lead to substantial value creation, as the market for cancer immunotherapies is rapidly growing. The specificity of their molecules for targets like MAGE-A4-pMHC could open up new avenues for personalized medicine in oncology. If these TCEs progress to clinical trials and demonstrate safety and efficacy, there could be significant partnerships and licensing deals on the horizon for AbCellera, which would likely impact the company's stock performance positively.
As an oncologist, the potential clinical applications of AbCellera's T-cell engagers are exciting. The ability to target specific solid tumor antigens while reducing the risk of cytokine release syndrome could be transformative for patient care. Current T-cell engaging therapies, like CAR-T, have shown remarkable results in hematologic malignancies but are often limited by severe toxicities in treating solid tumors.
AbCellera's TCEs could represent a significant advancement in oncology, offering a new line of attack for difficult-to-treat solid tumors. The focus on costimulatory CD28-binding antibodies could enhance the immune response without the toxicity typically seen with superagonists. If these findings translate into clinical success, it could mean a new arsenal of therapies for oncologists and improved outcomes for patients with cancers that are currently hard to treat.
Data show how AbCellera is expanding the reach of T-cell engagers with:
- CD3-binding antibodies that consistently generate T-cell engagers with potent tumor-cell killing and low cytokine release across multiple tumor targets, including PSMA, B7-H4, and 5T4
- Costimulatory CD28-binding antibodies that stimulate T cells without superagonist activity
- Highly specific T-cell engagers for the peptide-MHC target MAGE-A4
“TCEs are among the most promising new modalities in cancer therapy, but limitations in efficacy and safety have been barriers to realizing their potential for solid tumor indications,” said Bo Barnhart, Ph.D., VP, Translational Research at AbCellera. “Our data illustrate that we can repeatedly generate TCEs that maximize tumor-cell killing without inducing excessive cytokine release. Reducing the risk associated with CD3 engagement could improve efficacy both by widening the therapeutic window and by creating opportunities to further enhance potency through co-stimulatory modalities.”
AbCellera’s poster presentations, which are available for viewing here, describe how AbCellera is:
Widening the therapeutic window: AbCellera’s data describe the generation of TCEs for three solid tumor targets, PSMA, B7-H4, and 5T4, with functional profiles that are differentiated from clinical benchmarks. These molecules were engineered using a specific set of rare CD3-binding antibodies that consistently show potent tumor-cell killing and low cytokine release across multiple targets, demonstrating their potential to expand the therapeutic window across solid tumor indications.
Enhancing potency: TCEs that engage the CD28 costimulatory receptor can enhance T-cell activation, proliferation, and anti-tumor activities, particularly in solid tumors. The data show that AbCellera’s IgG and heavy chain-only CD28-binding antibodies do not display superagonist activity — a property associated with toxicity. Integrating costimulatory building blocks into AbCellera’s TCE repertoire may enable development of molecules with enhanced potency for difficult-to-treat cancers.
Broadening the accessible target space: The target repertoire for TCEs has been restricted to proteins expressed on the surface of cancer cells. Intracellular peptides displayed on MHC class I (pMHCs) would greatly expand the target pool for TCEs. However, development of TCEs against pMHCs has been limited due to the high degree of target specificity required. Data illustrate how AbCellera is unlocking this target class by generating molecules with high specificity for MAGE-A4-pMHC, which showed little to no binding to hundreds of off-target pMHCs.
“Our platform for creating precision TCEs to address indications in cancer and autoimmunity provides a strong foundation for both internal programs and strategic partnerships,” said Murray McCutcheon, Ph.D., SVP, Partnering at AbCellera. “We look forward to advancing these programs with the aim of delivering powerful new medicines for patients.”
About AbCellera’s T-Cell Engager Platform
CD3 T-cell engagers have the potential to be a cornerstone of cancer treatment. They guide the immune system to find and eliminate cancer cells by binding the CD3 protein on cancer-killing T cells and tumor targets at the same time. However, development of T-cell engagers has been limited due to challenges with efficacy and safety. To address these challenges, AbCellera developed a T-cell engager platform that includes novel CD3-binding antibodies to expand the therapeutic window for this modality, costimulatory building blocks to enhance efficacy for difficult-to-treat cancers, and discovery capabilities to broaden the range of T-cell engagers to complex peptide-MHC tumor targets. AbCellera is leveraging its platform to unlock the full potential of this modality and bring powerful new cancer medicines to patients.
About AbCellera Biologics Inc.
AbCellera (Nasdaq: ABCL) discovers and develops antibody medicines for indications across therapeutic areas including cancer, metabolic and endocrine conditions, and autoimmune disorders. AbCellera’s engine integrates technology, data science, infrastructure, and interdisciplinary teams to solve the most challenging antibody discovery problems. AbCellera is focused on advancing an internal pipeline of first-in-class and best-in-class programs and collaborating on innovative drug development programs with partners. For more information, please visit www.abcellera.com.
AbCellera Forward-Looking Statements
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Inquiries
Media: Kathleen Reid; media@abcellera.com, +1(236)521-6774
Business Development: Murray McCutcheon, Ph.D.; bd@abcellera.com, +1(604)559-9005
Investor Relations: Melanie Solomon; ir@abcellera.com, +1(778)729-9116
Source: AbCellera Biologics Inc.
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