Authors
Yanning Bao, Shengmin Yang, Yuan Ding, Jianfen Zhou, Xudong Zheng, Ruohan Chen, Zhixuan Jiang, Nana Meng, Dongsheng Pan, Jiasheng Lu, Jiacheng Guan, Jing Ye, Hongjia Zhu, Nan Xu, Cao Xie, Lei Yu, Linwei Lu, Weiyue Lu
Published in
Asian journal of pharmaceutical sciences. Volume 21. Issue 4. Pages 101175. Epub Jun 11, 2026.
Abstract
With low five-year survival estimates, poor prognosis, and high recurrence probabilities, glioma is considered one of the most intractable malignant tumors. Despite the discovery of lymphatic vascular system and immune system in the central nervous system (CNS), immune checkpoint blockade therapeutics, such as programmed death ligand 1 (PDL1, also called B7H1 or CD274) antibodies, are prevented from the CNS and glioma sites due to the existence of biological barriers including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). Herein, we constructed a BBB/BBTB-crossing recombinant antibody by fusing the PDL1 antibody (αPDL1) and the targeting moiety RAP22 peptide (RAP22) through a matrix metalloproteinase 2 (MMP2)-responsive cleavable linker, abbreviated as αPDL1-mRAP22. Not only was αPDL1-mRAP22 able to block PD1/PDL1 pathway, reduce T cell apoptosis, enhance T cell killing ability towards glioma cells in vitro, but also it showed higher accumulation in the glioma site, prolonged survival time, and potent immune responses as well as synergistic effects with temozolomide (TMZ) in vivo, offering a novel strategy for glioma immunotherapy.
PMID:
42548860
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.
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