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.
Keywords: Albumin; Aptamer; CTLA-4; Fexofenadine; Immune checkpoint blockade; Immunotherapy; Nanoparticle.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.