2023 World Conference on Lung Cancer (Posters)-P1.09. Characterization of the Expression of BTN1A1 Exclusive to PD-L1/PD-1 Axis in Small Cell Lung Cancer Using Spatial Biology Approach

P1.09. Characterization of the Expression of BTN1A1 Exclusive to PD-L1/PD-1 Axis in Small Cell Lung Cancer Using Spatial Biology Approach - PDF(Slides)

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A study conducted by STCube Pharmaceuticals and STCube, Inc. has characterized the expression of Butyrophilin 1A1 (BTN1A1) in relation to the PD-L1/PD-1 axis in small cell lung cancer (SCLC). BTN1A1 has been identified as a stress-inducible immune checkpoint protein with potential therapeutic implications for solid tumors. The study found that BTN1A1 and PD-L1 showed a mutually exclusive expression pattern in various tumor types, indicating that therapies targeting BTN1A1 could be promising for patients resistant to PD-1/PD-L1 inhibitors. <br /><br />The study also investigated the role of glycosylation in BTN1A1 stability. It was found that glycosylation-deficient mutants of BTN1A1 showed accelerated degradation compared to wild-type BTN1A1, highlighting the importance of glycosylation for BTN1A1 stability. <br /><br />Furthermore, the study developed a dimer- and glyco-specific anti-human BTN1A1 antibody called hSTC810. This antibody was found to recognize the dimerized form of BTN1A1 and showed no binding affinity for BTN1A1 in normal tissue contexts, making it a potential therapeutic tool. <br /><br />The efficacy of hSTC810 was then evaluated in a Phase 1 clinical trial, where it showed durable progression-free survival in patients with various tumor types, including small cell lung cancer. The study also found that the combination of hSTC810 and paclitaxel led to a decrease in spheroid size in SCLC cell cultures. <br /><br />Based on pharmacokinetic modeling and simulation, a dosing regimen of 800mg hSTC810 every 3 weeks was chosen for the Phase 1b/2 trial, along with paclitaxel. <br /><br />Overall, the study provides insight into the expression and stability of BTN1A1 in SCLC, as well as the potential therapeutic use of the antibody hSTC810. These findings pave the way for further clinical trials to evaluate the safety and efficacy of hSTC810 in combination with paclitaxel for the treatment of advanced solid tumors, including SCLC.

Asset Subtitle

Stephen Yoo

Meta Tag

Speaker Stephen Yoo

Topic Tumor Biology: Translational Biology - IO

Keywords

STCube Pharmaceuticals

STCube, Inc.

Butyrophilin 1A1

BTN1A1

PD-L1/PD-1 axis

small cell lung cancer

SCLC

immune checkpoint protein

glycosylation

hSTC810 antibody