Abstract
Introduction
Immune checkpoint blockade (ICB) is a promising strategy for cancer treatment and has generated remarkable clinical results against multiple malignancies. Exploration of new technical approaches to further boost the therapeutic efficacy of ICB is of potential medical importance. In this study, we designed a novel nanotherapeutics for ICB immunotherapy.
Methods
CTLA-4 aptamers were conjugated to the surface of albumin nanoparticle to construct an aptamer-modified nanostructure (Apt-NP). To improve ICB efficacy, fexofenadine (FEXO), an antihistamine, was encapsulated into Apt-NP to make a drug-loaded nanoparticle (Apt-NP-FEXO). The antitumor efficacies of Apt-NP and Apt-NP-FEXO were evaluated in vitro and in vivo.
Results
Apt-NP and Apt-NP-FEXO had average diameters of 149 nm and 159 nm, respectively. Similar to free CTLA-4 aptamers, Apt-modified NPs could selectively bind with CTLA-4 positive cells and improve lymphocyte-mediated antitumor cytotoxicity in vitro. In animal studies, compared with free CTLA-4 aptamer, Apt-NP significantly enhanced antitumor immunity. Moreover, Apt-NP-FEXO further improved antitumor efficacy vs. Apt-NP in vivo.
Conclusion
The results suggest that Apt-NP-FEXO represents a novel strategy to improve ICB outcome and may have application potential in cancer immunotherapy.
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All data generated or analyzed during this study is included in this published article.
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Funding
This work was supported by the Ministry of Science and Technology (2017YFA0205504), and the Tianjin Science and Technology Plan Project (22JCQNJC01590).
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XDY and FJY designed the research. FJY, YCA, XLL and ZY carried out the experiments and collected data. XDL provided technical expertise and support. FJY wrote the original manuscript. XDY revised the manuscript. All authors read and approved the final manuscript.
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PBMC was isolated from healthy donors. All donors were informed of the purpose of the experiment and required to sign an informed consent form. The procedure was approved by the Ethics Committee at Chinese Academy of Medical Sciences and Peking Union Medical College. The animal study was approved by the Ethical Committee of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. All animal procedures were approved by the committee on the Animal Care and Use of the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College and performed according to the Institutional Animal Care and Use guidelines.
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Yao, F., An, Y., Lai, X. et al. Novel nanotherapeutics for cancer immunotherapy by CTLA-4 aptamer-functionalized albumin nanoparticle loaded with antihistamine. J Cancer Res Clin Oncol 149, 7515–7527 (2023). https://doi.org/10.1007/s00432-023-04698-y
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DOI: https://doi.org/10.1007/s00432-023-04698-y