Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy

Abstract

As nano-sized materials prepared by isolating, disrupting and extruding cell membranes, cellular vesicles are emerging as a novel vehicle for immunotherapeutic drugs to activate antitumor immunity. Cell membrane-derived vesicles inherit the surface characteristics and functional properties of parental cells, thus having superior biocompatibility, low immunogenicity and long circulation. Moreover, the potent antitumor effect of cellular vesicles can be achieved through surface modification, genetic engineering, hybridization, drug encapsulation, and exogenous stimulation. The capacity of cellular vesicles to combine drugs of different compositions and functions in physical space provides a promising vehicle for combinational immunotherapy of cancer. In this review, the latest advances in cellular vesicles as vehicles for combinational cancer immunotherapy are systematically summarized with focuses on manufacturing processes, cell sources, therapeutic strategies and applications, providing an insight into the potential and existing challenges of using cellular vesicles for cancer immunotherapy.

Research progress in inducing immunogenic cell death of tumor cells

“…CV/D-S is a spherical particle with good stability and high biocompatibility, and its use enables adequate drug loading and safe delivery of DOX and SFN drugs in vivo . Owing to the tumor homing properties of these CVs, CV/D-S can accumulate in large quantities at the site of tumorigenesis and exert excellent antitumor properties, making it a promising drug delivery platform that can improve the effectiveness of multiple tumor treatments ( 198 , 199 , 227 ).…”

Biodegradable MnO2-based gene-engineered nanocomposites for chemodynamic therapy and enhanced antitumor immunity

“…Cell membrane-based vesicles have attracted widespread attention in recent years, which hold great promise for biomedical applications owing to their easy preparation and good biocompatibility [ [12] , [13] , [14] , [15] , [16] , [17] , [18] ]. In addition, they can be endowed with more functions by means of genetic engineering [ [19] , [20] , [21] , [22] ].…”

Dendritic Cell Membrane-Derived Nanovesicles for Targeted T Cell Activation

“…Exosomes secreted by antigen-presenting cells (APCs), namely, dendritic cells (DC), possess biologically functional MHC surface molecules presenting antigenic peptides (pMHC) capable of inducing antigen-specific T cell responses. ,,− When DCs are treated with tumor-associated antigens (TAAs), secreted exosomes retain the ability of parental DC to present these antigens and activate TAA-specific T cells, inducing a TAA-targeted response. ,,,, The function or immunomodulatory ability of exosomes can be further altered or enhanced through surface modification (e.g., amino conjugation, lipid insertion, and PEG (polyethylene glycol)-ylation) or genetic engineering of the parental cell or exosome itself to increase target specificity or load exogenous or endogenous molecules onto the exosome surface or interior. , Although exosome-based cancer immunotherapy has progressed, clinical application is hindered due to manufacturing constraints, such as low yields and a lack of scalable production, giving rise to investigation into alternative, exosome-mimicking platforms. ,− In an attempt to overcome these obstacles, synthetic alternatives to exosomes have been explored and include systems such as liposomes, dendrimers, nanogels, and metallic nanoparticles. Such systems may possess attributes that enable scalable production, high yields, customizable composition, or modifiable physiochemical properties but are hindered by cost and aggregation during storage and, due to their exogenous nature, lack intrinsic targeting capabilities and can be immunogenic or toxic. ,,,,− Biomimetic hybrid platforms that employ a synthetic nanoparticle core coated with a cell membrane have been proposed and possess desirable traits, as well as having shown favorable results in mice. , However, much like exosomes, such platforms are impeded by difficulty in achieving large-scale production, in addition to poor reproducibility and low efficiency in coating the nanoparticle core with cell membrane. , Cell-derived nanovesicles (CDNVs), which are artificially generated through fragmentation of cell membranes, have shown similar properties as exosomes, including target-specific cargo delivery and the incorporation of peptide-presenting MHC molecules on the CDNV surface to facilitate T cell activation via direct or indirect mechanisms. − Studies using dendritic cell-derived nanovesicles primarily focused on mediating T cell activation by inducing fusion or aggregation of CDNVs or by simultaneous treatment with CDNVs and free peptides.…”

“…Such systems may possess attributes that enable scalable production, high yields, customizable composition, or modifiable physiochemical properties but are hindered by cost and aggregation during storage and, due to their exogenous nature, lack intrinsic targeting capabilities and can be immunogenic or toxic. 13 , 16 , 25 , 29 , 31 − 34 Biomimetic hybrid platforms that employ a synthetic nanoparticle core coated with a cell membrane have been proposed and possess desirable traits, as well as having shown favorable results in mice. 35 , 36 However, much like exosomes, such platforms are impeded by difficulty in achieving large-scale production, in addition to poor reproducibility and low efficiency in coating the nanoparticle core with cell membrane.…”