Novel Complex of PD-L1 Aptamer and Albumin Enhances Antitumor Efficacy In Vivo.

Yacong An, Xundou Li, Fengjiao Yao, Jinhong Duan, Xian-Da Yang

Molecules (Basel, Switzerland) 2022 Feb 22

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The PD-1/PD-L1 pathway blockade can generate a good clinical response by reducing immunosuppression and provoking durable antitumor immunity. In addition to antibodies, aptamers can also block the interaction between PD-1 and PD-L1. For the in vivo application, however, free aptamers are usually too small in size and quickly removed from blood via glomerular filtration. To avoid renal clearance of aptamer, we conjugated the PD-L1 aptamer to albumin to form a larger complex (BSA-Apt) and evaluated whether BSA-Apt would enhance the in vivo antitumor efficacy. The PD-L1 aptamer was thiol-modified and conjugated to the amino group of BSA via a SMCC linker. The average size of BSA-Apt was 11.65 nm, which was above the threshold for renal clearance. Functionally, BSA-Apt retained the capability of the PD-L1 aptamer to bind with PDL1-expressing tumor cells. Moreover, both the free aptamer and BSA-Apt augmented the PBMC-induced antitumor cytotoxicity in vitro. Furthermore, BSA-Apt generated a significantly stronger antitumor efficacy than the free PD-L1 aptamer in vivo without raising systemic toxicity. The results indicate that conjugating the PD-L1 aptamer to albumin may serve as a promising strategy to improve the in vivo functionality of the aptamer and that BSA-Apt may have application potential in cancer immunotherapy.

Citation

Yacong An, Xundou Li, Fengjiao Yao, Jinhong Duan, Xian-Da Yang. Novel Complex of PD-L1 Aptamer and Albumin Enhances Antitumor Efficacy In Vivo. Molecules (Basel, Switzerland). 2022 Feb 22;27(5)