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Updated: Feb 20, 2026
Tracking Bispecific Antibody-Induced T Cell Trafficking Using Luciferase-Transduced Human T Cells
Published on: May 12, 2023
A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established solid tumors in
Timothy S Fisher1,2,3, Andrea T Hooper4,5, Justin Lucas4,5
1Oncology Research and Development Pfizer Inc., La Jolla, CA, USA. timothy.s.fisher@pfizer.com.
Abstract:
Strong evidence exists supporting the important role T cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. Recent clinical trials suggest that bispecific antibody-mediated retargeted T cells are a promising therapeutic approach to eliminate hematopoietic tumors. However, this approach has not been validated in solid tumors. PF-06671008 is a dual-affinity retargeting (DART®)-bispecific protein engineered with enhanced pharmacokinetic properties to extend in vivo half-life, and designed to engage and activate endogenous polyclonal T cell populations via the CD3 complex in the presence of solid tumors expressing P-cadherin. This bispecific molecule elicited potent P-cadherin expression-dependent cytotoxic T cell activity across a range of tumor indications in vitro, and in vivo in tumor-bearing mice. Regression of established tumors in vivo was observed in both cell line and patient-derived xenograft models engrafted with circulating human T lymphocytes. Measurement of in vivo pharmacodynamic markers demonstrates PF-06671008-mediated T cell activation, infiltration and killing as the mechanism of tumor inhibition.
Insights
This study shows PF-06671008, a bispecific antibody, effectively targets solid tumors by activating T cells. It demonstrated significant tumor regression in preclinical models, offering a new approach for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- T cells are crucial for anti-tumor immunity, but initiating specific responses against tumors is challenging.
- Bispecific antibodies retargeting T cells show promise for hematopoietic tumors but need validation in solid tumors.
Purpose of the Study:
- To evaluate PF-06671008, a novel bispecific antibody, for its efficacy against solid tumors expressing P-cadherin.
- To assess the molecule's ability to engage and activate endogenous T cells for tumor elimination.
Main Methods:
- PF-06671008, a dual-affinity retargeting (DART)-bispecific protein, was engineered for enhanced pharmacokinetics.
- In vitro and in vivo studies utilized tumor cell lines, patient-derived xenografts, and human T lymphocytes.
- Pharmacodynamic markers were measured to assess T cell activation, infiltration, and tumor killing.
Main Results:
- PF-06671008 demonstrated potent P-cadherin-dependent cytotoxic T cell activity in vitro and in vivo.
- Established tumors showed regression in xenograft models with human T lymphocytes.
- Pharmacodynamic analyses confirmed T cell activation, infiltration, and killing mediated by PF-06671008.
Conclusions:
- PF-06671008 is a promising bispecific molecule for targeting solid tumors expressing P-cadherin.
- The DART-bispecific protein effectively activates endogenous T cells, leading to tumor inhibition.
- This approach warrants further investigation as a potential cancer immunotherapy strategy.
