Whole‐Cell‐Mimicking Carrier‐Free Nanovaccines Amplify Immune Responses Against Cancer and Bacterial Infection

Abstract

Whole‐cell vaccines that provide broad‐spectrum antigens have been explored for recent decades. But so far, they have revealed limited success in clinical trials, possibly owing to their inefficiency in targeting immune organs and antigen‐presenting cells (APCs). Herein, a facile strategy is developed to convert the whole‐cell vaccines into the nanoscale size to promote their lymphatic migration and subsequent intracellular antigen presentation to maximize immune responses. Briefly, the study designs a multiple antigen delivery platform based on alum‐induced and cancer/bacterial cell membrane coated protein antigen nanoparticles. Through a simple two‐step vortex‐sonification method, a universal carrier‐free nano‐vaccine without additional excipients could be quickly fabricated. After subcutaneous vaccination, the developed nanovaccines rapidly migrate to lymph nodes, leading to their effective uptake by lymph node‐resident APCs, and subsequent antigen presentation and activation of downstream immune processes. Overall, the described promising work offers a safe, effective, facile, and widely applicable vaccine strategy, which has great potential for clinical transformation.

Cholesterol-deficient T cell membrane-encapsulated STING agonists for tumor-targeted immunotherapy

“…To prepare cell membrane, previously reported methods were used with some modification 31, 42 . Briefly, CTLL2, CTLL2-PD1 and CTLL2-PD1 treated with β-CD were collected and disrupted in hypotonic lysing buffer (pH 7.4, 20 mM Tris-HCl, 10 mM KCl, 2 mM MgCl 2 , Protease Inhibitor Cocktail) at 4 □ for 30 min.…”

Cholesterol removal significantly improves performance of a model anti-tumor biomimetic nano delivery system integrating immunotherapy and STING activation

“…To prepare cell membrane, previously reported methods were used with some modi cations 7,51 . Brie y, CTLL2, CTLL2-PD1 and CTLL2-PD1 treated with β-CD were collected and disrupted in hypotonic lysing buffer (pH 7.4, 20 mM Tris-HCl, 10 mM KCl, 2 mM MgCl 2 , Protease Inhibitor Cocktail) at 4 ℃ for 30 min.…”

Biomimetic Gold Nanostructure with a Virus-like Topological Surface for Enhanced Antigen Cross-Presentation and Antitumor Immune Response

“…22−24 It has been reported that particles with an intermediate size (10−100 nm in diameter) can both efficiently drain to regional draining lymph nodes and become retained there to increase the chance of antigen uptake and presentation by APCs. 25,26 Positively charged particles were also reported to be readily taken up into DCs due to the ionic attraction with the negatively charged cell membrane, which initiates efficient binding and facilitates particle internalization. 27,28 However, the effect of the particle topological structure on antigentargeted delivery has remained unexplored.…”

“…Because the uptake of antigen by DCs plays a critical role in the induction of innate and adaptive immunity, the delivery systems that not only can protect the antigens from degradation , but also can facilitate the interaction with DCs would be a promising strategy for vaccine development. The physicochemical characteristics of particles, such as the size, surface properties, rigidity, and shape, all significantly influence the in vivo trafficking and cellular internalization. − It has been reported that particles with an intermediate size (10–100 nm in diameter) can both efficiently drain to regional draining lymph nodes and become retained there to increase the chance of antigen uptake and presentation by APCs. , Positively charged particles were also reported to be readily taken up into DCs due to the ionic attraction with the negatively charged cell membrane, which initiates efficient binding and facilitates particle internalization. , However, the effect of the particle topological structure on antigen-targeted delivery has remained unexplored. Thus, understanding how the topological structure influences immune responses can greatly aid in the rational design of better vaccines.…”