Thermoresponsive Polypeptide Fused L-Asparaginase with Mitigated Immunogenicity and Enhanced Efficacy in Treating Hematologic Malignancies.

ABSTRACT: L-Asparaginase (ASP) is well-known for its excellent efficacy in treating hematological malignancies. Unfortunately, the intrinsic shortcomings of ASP, namely high immunogenicity, severe toxicity, short half-life, and poor stability, restrict its clinical usage. Poly(ethylene glycol) conjugation (PEGylation) of ASP is an effective strategy to address these issues, but it is not ideal in clinical applications due to complex chemical synthesis procedures, reduced ASP activity after conjugation, and pre-existing anti-PEG antibodies in humans. Herein, the authors genetically engineered an elastin-like polypeptide (ELP)-fused ASP (ASP-ELP), a core-shell structured tetramer predicted by AlphaFold2, to overcome the limitations of ASP and PEG-ASP. Notably, the unique thermosensitivity of ASP-ELP e

SUBMITTER: Zhang S 

PROVIDER: S-EPMC10427413 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature