Dendritic Cell Membrane-Derived Nanovesicles for Targeted T Cell Activation

Abstract

T cells play an integral role in the generation of an effective immune response and are responsible for clearing foreign microbes that have bypassed innate immune system defenses and possess cognate antigens. The immune response can be directed toward a desired target through the selective priming and activation of T cells. Due to their ability to activate a T cell response, dendritic cells and endogenous vesicles from dendritic cells are being developed for cancer immunotherapy treatment. However, current platforms, such as exosomes and synthetic nanoparticles, are limited by their production methods and application constraints. Here, we engineer nanovesicles derived from dendritic cell membranes with similar properties as dendritic cell exosomes via nitrogen cavitation. These cell-derived nanovesicles are capable of activating antigen-specific T cells through direct and indirect mechanisms. Additionally, these nanovesicles can be produced in large yields, overcoming production constraints that limit clinical application of alternative immunomodulatory vesicle or nanoparticle-based methods. Thus, dendritic cell-derived nanovesicles generated by nitrogen cavitation show potential as an immunotherapy platform to stimulate and direct T cell response.

Exosome-like Systems: From Therapies to Vaccination for Cancer Treatment and Prevention—Exploring the State of the Art

“…In the cross-dressing method, after APCs receive exosomes, they begin to process these antigens and present them to CD8 + T-cells. In a study conducted by Harvey et al, the direct and indirect mechanisms of CD8 + T-cell activation by cell-derived nanovesicles (CDNVs) were evaluated [90]. Initially, they activated DCs using IFN-G and introduced the SIINFEKL peptide to produce CDNVs expressing the MHC-I ligand.…”

Bioinspired cellular membrane-derived vesicles for mRNA delivery

“…Top-down strategies involve the creation of artificial exosomes starting from the cellular level. The main methods include extrusion, microfluidics, ultrasound, chemical induction, and nitrogen cavitation [40][41][42][43]. While top-down strategies can yield a substantial number of exosome analogs, enhancing the overall yield, the production process tends to be more time-consuming.…”

Exosome-Like Systems: From Therapies to Vaccination for Cancer Treatment and Prevention—Exploring the State of the Art

“…In the cross-dressing method, after APCs receive exosomes, they begin to process these antigens and present them to CD8 + T-cells. In a study conducted by Harvey et al, the direct and indirect mechanisms of CD8 + T-cell activation by cell-derived nanovesicles (CDNVs) were evaluated [88]. Initially, they activated DCs using IFN-ɣ and introduced the SIINFEKL peptide to produce CDNVs expressing MHC-I ligand.…”