超长效 L-天冬酰胺酶联合免疫检查点抑制剂实现转移性实体瘤的饥饿免疫协同治疗

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研究内容简介 Visual representation of starvation-immunotherapy enabled by ASNase-ELP in conjunction with aPD-1. (a) The biosynthetic route of ASNase-ELP, wherein AlphaFold2 predicted the structures of ELP, ASNase, and ASNase-ELP. (b) Enhanced anti-metastatic efficacy of starvation-immunotherapy. ASNase-ELP precipitates out to form a reservoir upon intratumoral injection. The sustained dissolution of ASNase-ELP in the reservoir leads to its durable diffusion into the tumor tissue and the circulatory system. The activ e form of ASNase-ELP efficiently catabolizes Asn, selectively inducing the death of tumor cells. Concurrently, aPD-1 blocks the binding of PD-1 to its corresponding receptor, PD-L1, and facilitates the recognition of major histocompatibility complex class I (MHC-I) molecules by the T-cell receptor (TCR). Consequently, aPD-1 activation elicits a robust immune response against the tumor cells, which works with the starvation mechanism to enhance anti-metastatic effectiv ………………………………