Unlocking the Potential of AB154: Advancing Combination Cancer Immunotherapies with a Humanized Anti-TIGIT Antibody

3 June 2024
TIGIT is an inhibitory receptor on NK cells, CD8+ T-cells, and Treg cells, which competes with the activating receptor DNAM-1 for binding to shared ligands CD155 and CD112 expressed on tumor and antigen-presenting cells. High TIGIT expression is associated with immune suppression and is often seen alongside upregulation of other immune checkpoint proteins and T-cell exhaustion markers like PD-1 in progressing malignancies.

AB154 is a fully humanized antibody developed to inhibit TIGIT, thereby promoting a more effective anticancer immune response. It has been shown to block human TIGIT with high affinity and, when combined with anti-PD-1 or anti-PD-L1 in mixed lymphocyte reactions, significantly increased IFN-gamma secretion, indicating a synergistic effect.

Data from TCGA indicates co-expression of TIGIT and PD-1 in various tumor types, with upregulation compared to normal tissue. Immunophenotyping of human tumor-infiltrating lymphocytes revealed a strong correlation between TIGIT and PD-1 co-expression on CD8+ T-cells and Treg cells.

A multicolor flow cytometry-based assay was developed to evaluate the pharmacodynamic effects of AB154, demonstrating complete inhibition of TIGIT in human whole blood and suitable target engagement by AB154 in blood mononuclear cells. Additionally, TIGIT receptor occupancy by AB154 in NSCLC patients treated with pembrolizumab was comparable to that in healthy donors.

The findings support the combination of AB154 with the in-house anti-PD-1 antibody AB122 for upcoming clinical trials and provide a methodology for evaluating TIGIT receptor occupancy in AB154 dose escalation studies. AB154 is anticipated to enter clinical trials in 2018.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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Click on the image below to go directly to the Translational Medicine search interface.

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