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Updated: May 25, 2026
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Autologous T-cell antigen coupler targeting HER2 (TAC01-HER2) in advanced or metastatic solid tumors
Ecaterina E Dumbrava1, Daniel Olson2, Mohamed A Gouda1
1The Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Background:
The T-cell antigen coupler (TAC) is a novel genetically engineered receptor that recruits the native T-cell receptor upon recognition of an antigen. The downstream activation of TAC T cells has been effective against tumors in preclinical models and is safer than chimeric antigen receptor T cells. Human epidermal growth factor receptor 2 (HER2) is a validated biomarker for cancer-targeted therapy, but cell therapy approaches have been met with unmanageable toxicity.
Patients And Methods:
We designed a phase I clinical trial of TAC01-HER2, an autologous T-cell product that targets HER2, in patients with HER2-positive advanced solid tumors. The trial had a dose-escalation phase and dose expansion at the recommended phase II dose (RP2D).
Results:
A total of 23 patients with HER2-positive solid tumors were enrolled in this study. The most common treatment-related adverse events (AEs) were cytokine release syndrome (n = 14, 60.9%), anemia (n = 5, 21.7%), and increased alanine aminotransferase (n = 5, 21.7%). The RP2D was 6-8 × 106 cells/kg. No treatment-related deaths or AEs leading to study discontinuation were reported. Two of nine patients with gastric and gastroesophageal junction (GEJ) cancers had partial responses (PRs), and the disease control rate (stable disease or PR) was 61.1% in the 18 patients with evaluable tumors. The median progression-free survival was 2.6 months (range 0.8-12.4), and the overall survival rate at 6 months was 57.9% (95% confidence interval 36.3% to 76.9%). Persistence of TAC T cells in peripheral blood was observed in all patients until at least day 29 after the first infusion.
Conclusion:
We demonstrated that treatment with TAC T cells was safe, feasible, and well-tolerated. TAC01-HER2 showed manageable toxicity and early efficacy for patients with HER2-positive gastric, GEJ, or esophageal adenocarcinoma who have undergone extensive previous treatments. These results suggest that TAC may offer a promising approach to control T-cell activity through cellular therapy.
Insights
T cell antigen coupler (TAC) therapy using TAC01-HER2 demonstrated safety and feasibility in patients with HER2-positive advanced solid tumors. This novel cell therapy showed manageable toxicity and promising early efficacy, suggesting a new approach for cancer treatment.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- T cell antigen coupler (TAC) is a novel engineered receptor that recruits native T cell receptors for antigen recognition.
- TAC T cells show preclinical efficacy and improved safety over chimeric antigen receptor T cells.
- Human epidermal growth factor receptor 2 (HER2) is a target in cancer therapy, but cell therapies face toxicity challenges.
Purpose of the Study:
- To evaluate the safety, feasibility, and preliminary efficacy of TAC01-HER2 in patients with HER2-positive advanced solid tumors.
- To determine the recommended phase 2 dose (RP2D) for TAC01-HER2 therapy.
Main Methods:
- Phase 1 clinical trial with dose-escalation and dose-expansion phases.
- Autologous T cell product (TAC01-HER2) administered to patients with HER2-positive solid tumors.
- Monitoring of treatment-related adverse events, efficacy endpoints, and T cell persistence.
Main Results:
- 23 patients enrolled; RP2D established at 6-8 × 10^6 cells/kg.
- Most common adverse events included cytokine release syndrome (60.9%) and anemia (21.7%); no treatment-related deaths.
- Partial responses observed in 2/9 gastric/GEJ cancer patients; disease control rate of 61.1% in evaluable patients. Median progression-free survival was 2.6 months; 6-month overall survival rate was 57.9%.
- TAC T cell persistence observed in all patients up to day 29.
Conclusions:
- TAC01-HER2 treatment is safe, feasible, and well-tolerated in patients with HER2-positive advanced solid tumors.
- The therapy demonstrated manageable toxicity and early signs of efficacy in heavily pre-treated patients with gastric, GEJ, or esophageal adenocarcinoma.
- TAC T cells represent a promising cellular therapy approach for controlling T cell activity in cancer treatment.
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