Abstract

Background

Immune checkpoint blockade (ICB) is a promising strategy for cancer treatment and has achieved remarkable clinical results. Further improvement of ICB efficacy may advance cancer immunotherapy and has evident medical importance. Here in this study, a PD-1 aptamer was functionalized with a tumor-homing nucleolin aptamer (AS1411) to build a novel bispecific agent (BiApt) for boosting the efficacy of ICB therapy.

Results

The two aptamers were coupled together via sticky ends to form BiApt, which had an average size of 11.70 nm. Flow cytometry revealed that BiApt could bind with both the activated T cells and the nucleolin-expressing tumor cells. In addition, BiApt could recruit more T cells to the vicinity of nucleolin-positive tumor cells. Functionally, BiApt enhanced the PBMC-mediated anticancer cytotoxicity in vitro compared with free PD-1 aptamer. Moreover, in an animal model of CT26 colon cancer, BiApt significantly boosted the antitumor efficacy vs. free PD-1 aptamer.

Conclusion

The results suggest that bispecific agent combining ICB and tumor-homing functions has potential to improve the efficacy of ICB immunotherapy.

Details

Title
Novel bispecific aptamer targeting PD-1 and nucleolin for cancer immunotherapy
Author
Fu, Junjun 1 ; Yao, Fengjiao 1 ; An, Yacong 1 ; Li, Xundou 1 ; Wang, Wenya 2 ; Yang, Xian-Da 1 

 Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Basic Medical Sciences, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839) 
 Beijing Qinghua Hospital, Beijing, China (GRID:grid.506261.6) 
Pages
27
Publication year
2023
Publication date
Dec 2023
Publisher
Springer Nature B.V.
ISSN
18686958
e-ISSN
18686966
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2791791772
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.