Publications by authors named "Shoichi Metsugi"
Antibodies are one of the predominant treatment modalities for various diseases. To improve the characteristics of a lead antibody, such as antigen-binding affinity and stability, we conducted comprehensive substitutions and exhaustively explored their sequence space. However, it is practically unfeasible to evaluate all possible combinations of mutations owing to combinatorial explosion when multiple amino acid residues are incorporated.
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- Molecular evolution is key for developing effective therapeutic antibodies, but traditional methods for improving their affinity are expensive and time-consuming due to numerous mutation experiments.
- A long short term memory network (LSTM) was utilized to streamline the discovery of high-affinity antibody sequences, specifically targeting kynurenine, a compound linked to niacin synthesis.
- The LSTM model effectively predicted antibody sequences that demonstrated over 1800 times higher binding affinity than the original version, outperforming conventional frequency-based screening methods.
Article Synopsis
- - The study discusses STA551, a novel anti-CD137 switch antibody that activates only in the presence of extracellular adenosine triphosphate (exATP), focusing on its potential to overcome limitations seen in previous CD137 agonists which suffered from toxicity and specificity issues.
- - STA551 showed strong antitumor effects across various mouse and human tumor models without causing systemic immune activation, indicating a wide therapeutic window and good tolerability even at high doses in monkeys.
- - The findings suggest STA551 could be a promising treatment option for a broad range of cancers, as it does not rely on specific tumor antigens for efficacy, paving the way for its clinical testing and future developments in cancer therapy.
TSC1 acts coordinately with TSC2 in a complex to inhibit mTOR, an emerging therapeutic target and known promoter of cell growth and cell cycle progression. Perturbation of the mTOR pathway, through abnormal expression or function of pathway genes, could lead to tumorigenesis. TSC1 and TSC2 expression is reduced in invasive breast cancer as compared with normal mammary epithelium.
View Article and Find Full Text PDFThe motile mechanism of remains unknown but is believed to differ from any previously identified mechanism in bacteria. Gli349 of is known to be responsible for both adhesion to glass surfaces and mobility. We therefore carried out sequence analyses of Gli349 and its homolog MYPU2110 from to decipher their structures.
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