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Updated: Jul 18, 2025
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Preclinical development of 1B7/CD3, a novel anti-TSLPR bispecific antibody that targets CRLF2-rearranged Ph-like
Ze Tian1, Chunhua Shi2, Guojun Yang2
1ORBIT Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ztian1@mdanderson.org.
Abstract:
Patients harboring CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) face a 5-year survival rate as low as 20%. While significant gains have been made to position targeted therapies for B-ALL treatment, continued efforts are needed to develop therapeutic options with improved duration of response. Here, first we have demonstrated that patients with CRLF2-rearranged Ph-like ALL harbor elevated thymic stromal lymphopoietin receptor (TSLPR) expression, which is comparable with CD19. Then we present and evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR. In vitro, 1B7/CD3 exhibits optimal binding to both human and cynomolgus CD3 and TSLPR. Further, 1B7/CD3 was shown to induce potent T cell activation and tumor lytic activity in both cell lines and primary B-ALL patient samples. Using humanized cell- or patient-derived xenograft models, 1B7/CD3 treatment was shown to trigger dose-dependent tumor remission or growth inhibition across donors as well as induce T cell activation and expansion. Pharmacokinetic studies in murine models revealed 1B7/CD3 to exhibit a prolonged half-life. Finally, toxicology studies using cynomolgus monkeys found that the maximum tolerated dose of 1B7/CD3 was ≤1 mg/kg. Overall, our preclinical data provide the framework for the clinical evaluation of 1B7/CD3 in patients with CRLF2-rearranged B-ALL.
Insights
A novel bispecific antibody, 1B7/CD3, shows promise for treating CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL). This therapy targets thymic stromal lymphopoietin receptor (TSLPR) and demonstrates potent anti-tumor activity in preclinical models.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- CRLF2-rearranged B-lineage acute lymphocytic leukemia (B-ALL) has a poor prognosis with a 5-year survival rate as low as 20%.
- Current targeted therapies for B-ALL require further development for improved response duration.
- Elevated thymic stromal lymphopoietin receptor (TSLPR) expression is observed in patients with CRLF2-rearranged Ph-like ALL.
Purpose of the Study:
- To evaluate the anti-tumor characteristics of 1B7/CD3, a novel CD3-redirecting bispecific antibody (BsAb) that co-targets TSLPR.
- To assess the efficacy and safety of 1B7/CD3 in preclinical models of CRLF2-rearranged B-ALL.
Main Methods:
- In vitro assessment of 1B7/CD3 binding to human and cynomolgus CD3 and TSLPR.
- Evaluation of T cell activation and tumor lytic activity induced by 1B7/CD3 in cell lines and primary B-ALL samples.
- In vivo studies using humanized cell- or patient-derived xenograft models, pharmacokinetic, and toxicology studies in murine and cynomolgus monkey models.
Main Results:
- 1B7/CD3 demonstrated potent T cell activation and tumor lytic activity in vitro.
- 1B7/CD3 treatment led to dose-dependent tumor remission or growth inhibition in xenograft models.
- Pharmacokinetic studies showed a prolonged half-life, and toxicology studies established a maximum tolerated dose of ≤1 mg/kg in cynomolgus monkeys.
Conclusions:
- Preclinical data support the clinical evaluation of 1B7/CD3 for CRLF2-rearranged B-ALL.
- 1B7/CD3 exhibits promising anti-tumor activity and a favorable safety profile.
- This novel bispecific antibody offers a potential new therapeutic option for patients with refractory B-ALL.
