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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.
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Details
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)
2 Beijing Qinghua Hospital, Beijing, China (GRID:grid.506261.6)