PROTEINA
PROTEINA Co., Ltd., in collaboration with Seoul National University (SNU) and Seoul National University Hospital (SNUH), has announced the publication of its latest research in Nature Biomedical Engineering. The study presents a novel approach to personalizing treatment for acute myeloid leukemia (AML) patients by leveraging protein-protein interaction (PPI) profiling to predict drug response.
Critical Need for Personalized AML Treatment
Nearly 90% of AML patients fail to survive without achieving complete remission during initial treatment. ABT-199, in combination with hypomethylating agents, has emerged as a promising therapy by inhibiting the BCL2 protein, a key player in cancer progression. However, varying patient dependency on BCL2 signaling complicates patient selection for this treatment.
Innovative Technique for PPI Profiling
A team of researchers from PROTEINA, SNU, and SNUH tackled this challenge by developing a single-molecule pull-down and co-immunoprecipitation (SMPC) technique. This method quantifies over 20 different types of PPIs and protein expression levels from clinical specimens, using as little as 1 ml of body fluid such as blood or bone marrow aspirate.
The SMPC technique identifies critical PPI links contributing to leukemia cell survival when ABT-199 is administered. The researchers created a prediction model with an AUROC value of 0.94, accurately selecting patients likely to respond to ABT-199 therapy.
Key Findings and Clinical Implications
The study revealed that the BCL2-BAX complex plays a significant role in the survival of AML cells under apoptotic stress induced by ABT-199. Conversely, the BCLxL-BAK complex is linked to resistance, highlighting the drug's selective mechanism.
Through extensive PPI profiling of samples from 32 AML patients, the research identified key PPIs correlating with drug responsiveness. The developed biomarker demonstrated high predictive power, forecasting drug response in 9 out of 10 patients with a sensitivity of 100% and specificity of 83.3%.
Future Directions and Clinical Validation
PROTEINA has acquired venetoclax response prediction technology and patents from SNU and SNUH. The company is currently collaborating with Professor Janghee Woo of Emory University School of Medicine for global clinical validation. "We are thrilled to start this large-scale clinical validation, which is a significant step toward expanding the utility of our platform technology in precision medicine," says Hongwon Lee, Chief Technology Officer at PROTEINA.
Support and Acknowledgements
This research was supported by the National Grants for Leading Scientists of the National Research Foundation of South Korea (NRF) [grant number NRF-2021R1A3B1071354], the Bio Medical Technology Development Program of the NRF [grant number NRF-2018M3A9E2023523], and the Korea Health Technology R&D Project of the Korea Health Industry Development Institute (KHIDI) [grant number HI14C1277].
About PROTEINA Co., Ltd.
PROTEINA Co., Ltd. is a leading biotech company specializing in proteomics, focusing on protein complexes and protein-protein interactions. The company provides cutting-edge analysis services for large pharmaceutical developers, aiming to advance precision medicine through innovative diagnostic technologies.
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