AbCellera Presents Promising Preclinical Data Demonstrating Efficacy of PSMA x CD3 T-Cell Engagers at AACR 2025
AbCellera Biologics Inc. (Nasdaq: ABCL), a leading technology company specializing in the discovery and development of antibody-based therapeutics, has unveiled compelling preclinical data supporting the efficacy of its PSMA x CD3 T-cell engager program during a presentation at the American Association for Cancer Research (AACR) Annual Meeting 2025. The data, which focus on a novel bispecific T-cell engager targeting Prostate-Specific Membrane Antigen (PSMA), demonstrate potent anti-tumor activity and support the advancement of this candidate toward clinical development for the treatment of prostate cancer.
The findings mark a key milestone in AbCellera’s growing oncology pipeline and underscore the company’s strategy to apply its full-stack antibody discovery and development platform to address difficult-to-treat cancers with high unmet medical need. Presented in a poster session at AACR 2025, the study detailed the in vitro and in vivo performance of the PSMA x CD3 bispecific molecule, highlighting its tumor-killing capabilities, selectivity, and pharmacological profile.
A Targeted Approach to Prostate Cancer
Prostate cancer remains one of the most commonly diagnosed cancers in men and a leading cause of cancer-related mortality worldwide. While early-stage prostate cancer can often be managed with conventional therapies, treatment options become increasingly limited in advanced stages of the disease, particularly in metastatic castration-resistant prostate cancer (mCRPC). PSMA is a clinically validated tumor-associated antigen that is overexpressed in the majority of prostate cancer cells, making it an attractive target for therapeutic intervention.
AbCellera’s PSMA x CD3 T-cell engager is designed to leverage the specificity of PSMA targeting and the potent immune-mediated killing potential of CD3 engagement on T cells. By bridging tumor cells and T cells, the bispecific antibody enables the formation of immunological synapses that result in direct T-cell activation and tumor cell lysis. This approach holds the potential to convert immunologically “cold” tumors into “hot” tumors that are responsive to immune attack.
Preclinical Efficacy Demonstrated
In a series of preclinical studies, AbCellera’s research team evaluated the efficacy and safety of its PSMA x CD3 T-cell engager using multiple prostate cancer cell lines and in vivo mouse models. Key highlights from the AACR 2025 presentation include:
- Potent In Vitro Cytotoxicity: The bispecific antibody induced robust T-cell activation and dose-dependent killing of PSMA-positive cancer cell lines at low picomolar concentrations. The molecule demonstrated minimal activity against PSMA-negative cells, indicating strong selectivity and a favorable therapeutic index.
- In Vivo Tumor Regression: In humanized mouse models bearing PSMA-expressing prostate tumors, treatment with the PSMA x CD3 bispecific led to rapid and sustained tumor regression. A single administration produced durable responses without significant toxicity or cytokine release syndrome (CRS).
- Favorable Pharmacokinetics: The molecule exhibited extended half-life and retained functional stability in circulation, which may reduce the need for frequent dosing in a clinical setting. Pharmacokinetic studies in rodents and non-human primates support a profile suitable for further translational development.
- Low Risk of Cytokine Release: Importantly, in vitro T-cell activation assays showed that the antibody induced lower levels of pro-inflammatory cytokines compared to benchmark molecules. This suggests a reduced likelihood of immune-related adverse events—a common challenge with CD3 bispecifics.
Dr. Estelle Merriweather, Vice President of Translational Oncology at AbCellera, noted, “Our PSMA x CD3 T-cell engager is the result of an end-to-end discovery campaign using our integrated platform, which enables precise control over epitope targeting, T-cell activation, and manufacturability. These data reinforce our confidence in the candidate’s potential to address critical gaps in prostate cancer treatment.”
Differentiation Through Advanced Engineering
Unlike traditional antibody development processes, AbCellera’s platform combines high-throughput single-cell screening, AI-powered antibody engineering, and advanced in silico modeling to optimize therapeutic candidates across multiple dimensions simultaneously. For its PSMA x CD3 program, the company screened thousands of antibody pairs to identify the optimal combination of tumor targeting and immune activation.
Additionally, the bispecific format employed in this molecule incorporates proprietary engineering to improve T-cell redirection while minimizing off-target effects. This includes tuning the CD3 binding arm to limit systemic activation and reduce the risk of cytokine storm—a critical safety consideration in T-cell engagers.
The use of IgG-like scaffolds and Fc engineering further enhances the molecule’s pharmacokinetics and manufacturability, which are often challenging in bispecific drug development. According to company scientists, the candidate maintains high expression levels and stability during large-scale production, positioning it well for downstream development.
A Strategic Focus on Oncology
The PSMA x CD3 program is part of AbCellera’s expanding internal pipeline of immune-oncology candidates. In recent years, the company has increasingly invested in developing its own clinical-stage assets, leveraging its platform to go beyond discovery and into full therapeutic development. The oncology pipeline now includes multiple bispecifics, checkpoint inhibitors, and novel immune modulators targeting both solid tumors and hematological malignancies.
“Bringing our PSMA x CD3 candidate to AACR underscores our commitment to delivering new treatment options for cancer patients by accelerating innovation from the lab to the clinic,” said Carl Hansen, Ph.D., CEO and President of AbCellera. “We believe that our platform gives us the ability to overcome the historical limitations of T-cell engagers and generate safer, more effective therapies.”
Hansen also emphasized the company’s integrated approach, which includes capabilities from early discovery through IND-enabling studies, CMC development, and clinical trial planning. “As we move toward IND submission, we’re focused on building a strong foundation for first-in-human studies,” he added.
Next Steps: Advancing to the Clinic
Following the successful presentation at AACR 2025, AbCellera plans to complete IND-enabling studies and submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in the second half of 2025. The company aims to initiate a Phase 1 clinical trial in patients with advanced PSMA-positive prostate cancer by early 2026.
The Phase 1 trial will evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the PSMA x CD3 T-cell engager, with particular focus on identifying a recommended dose for expansion cohorts. Patient selection will incorporate PSMA expression profiling to maximize the likelihood of response.
AbCellera is also exploring potential partnerships for global development and commercialization, as well as opportunities to combine the PSMA x CD3 bispecific with other immunotherapies such as checkpoint inhibitors or tumor-targeting cytokines.
