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. 2024 Aug 20:137:112393.
doi: 10.1016/j.intimp.2024.112393. Epub 2024 Jun 8.

A PD-L1 tropism-expanded oncolytic adenovirus enhanced gene delivery efficiency and anti-tumor effects

Shengsheng Mei  1 , Shanshan Peng  1 , Eu Gene Vong  1 , Jinbiao Zhan  2
Affiliations

A PD-L1 tropism-expanded oncolytic adenovirus enhanced gene delivery efficiency and anti-tumor effects

Shengsheng Mei et al. Int Immunopharmacol. .

Abstract

Recombinant adenovirus serotype 5 (Ad5)-mediated virotherapy is a maturing technique in cancer treatment. However, the utility of adenovirus (Ad) has been limited by low expression of coxsackievirus and adenovirus receptor (CAR) in cancer cells resulting in poor infectivity of Ads. To overcome the problem, we aimed to develop a novel tropism-modified oncolytic adenovirus, ZD55-F-HI-sPD-1-EGFP, which contains the epitope of PD-1 (70-77aa) at the HI-loop of Ad fiber. Trimerization of Fiber-sPD-1 was confirmed by immunoblot analysis. ZD55-F-HI-sPD-1-EGFP shows a remarkable improvement in viral infection rate and gene transduction efficiency in the PD-L1-positive cancer cells. Competition assays with a PD-L1 protein reveals that cell internalization of ZD55-F-HI-sPD-1-EGFP is mediated by both CAR and PD-L1 at a high dose. The progeny virus production capacity showed that sPD-1 incorporated fiber-modified oncolytic Ad replication was not affected. Furthermore, treating with ZD55-F-HI-sPD-1-EGFP significantly increased viral infection rate and enhanced anti-tumor effect in vivo. This study demonstrates that the strategy to expand tropism of oncolytic Ad may significantly improve therapeutic profile for cancer treatment.

Keywords: Oncolytic adenovirus; PD-L1 tropism-expanded; Viral infectivity; sPD-1.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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