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Updated: Jan 31, 2026
Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Enhancing anti-tumor immunity through co-blocking PD-L1 and TIGIT by facilitating tumor-directed responses and
Xi Zhu1, Xiaopei Cui1, Haijia Yu1
1Drug Discovery, Shanghai Huaota Biopharmaceutical Co. Ltd., Shanghai, China.
Abstract:
Combination therapy targeting the PD-1/PD-L1 and TIGIT pathways has been explored to enhance the efficacy of current immunotherapies. In this study, we investigated strategies to further potentiate the co-blockade of PD-L1 and TIGIT for cancer immunotherapy. Firstly, we demonstrated that the bispecific antibody (HB0036) for PD-L1 and TIGIT co-blockade induced a greater T-cell proliferative response in vitro compared to the combined administration of the parental antibodies. This response was associated with CD226 upregulation and PD-1 downregulation. HB0036 significantly enriched the TIGIT antibody at PD-L1+ tumors and achieved improved tumor control with favorable immunological characteristics in both syngeneic and xenograft tumor models. Secondly, we showed that tumor control by co-targeting PD-L1 and TIGIT can be further enhanced by additionally blocking VEGF, a key player in tumorigenesis and tumor angiogenesis, in preclinical studies. Lastly, considering the heterogeneity of tumors, we analyzed how the expression patterns of PD-L1 and CD155 influence T cell responses. We also examined the spatial distribution of PD-L1 and CD155, along with related immunological parameters from patient samples, to assess the potential of PD-L1 and TIGIT co-blockade in diverse tumor contexts.
Insights
A novel bispecific antibody targeting PD-L1 and TIGIT pathways enhances cancer immunotherapy by boosting T-cell responses. Combining this with VEGF blockade further improves tumor control, showing promise for diverse cancer types.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Current immunotherapies targeting PD-1/PD-L1 pathways show promise but can be enhanced.
- TIGIT pathway blockade is another strategy explored to improve anti-cancer immunity.
- Co-blockade of PD-L1 and TIGIT pathways offers a potential strategy to overcome limitations of single-target therapies.
Purpose of the Study:
- To investigate strategies for potentiating the co-blockade of PD-L1 and TIGIT pathways in cancer immunotherapy.
- To evaluate a bispecific antibody (HB0036) targeting both PD-L1 and TIGIT.
- To explore combination therapies involving PD-L1/TIGIT co-blockade with VEGF inhibition and analyze patient sample data.
Main Methods:
- In vitro assessment of T-cell proliferation in response to bispecific antibody (HB0036) versus parental antibodies.
- In vivo studies using syngeneic and xenograft tumor models to evaluate tumor control and immunological characteristics.
- Preclinical evaluation of combining PD-L1/TIGIT co-blockade with VEGF inhibition.
- Analysis of PD-L1, CD155 expression, and spatial distribution in patient tumor samples.
Main Results:
- The bispecific antibody HB0036 induced greater T-cell proliferation in vitro compared to combined parental antibodies, associated with CD226 upregulation and PD-1 downregulation.
- HB0036 demonstrated improved tumor control and favorable immunological profiles in preclinical models.
- Co-targeting PD-L1 and TIGIT with VEGF blockade further enhanced tumor control in preclinical studies.
- Analysis of patient samples provided insights into the influence of PD-L1 and CD155 expression patterns and spatial distribution on T-cell responses.
Conclusions:
- Bispecific antibody-mediated co-blockade of PD-L1 and TIGIT is a potent strategy for enhancing cancer immunotherapy.
- Combination therapy with VEGF inhibition offers further improvements in tumor control.
- Understanding tumor heterogeneity and immune cell interactions is crucial for optimizing PD-L1 and TIGIT co-blockade efficacy across diverse cancer types.
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