Dexosomes as a cell-free vaccine for cancer immunotherapy
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(2020) 39:258
REVIEW
Open Access
Dexosomes as a cell-free vaccine for cancer immunotherapy Sepideh Nikfarjam1, Jafar Rezaie2, Fatah Kashanchi3* and Reza Jafari2,4*
Abstract Dendritic cells (DCs) secrete vast quantities of exosomes termed as dexosomes. Dexosomes are symmetric nanoscale heat-stable vesicles that consist of a lipid bilayer displaying a characteristic series of lipid and protein molecules. They include tetraspanins and all established proteins for presenting antigenic material such as the major histocompatibility complex class I/II (MHC I/II) and CD1a, b, c, d proteins and CD86 costimulatory molecule. Dexosomes contribute to antigen-specific cellular immune responses by incorporating the MHC proteins with antigen molecules and transferring the antigen-MHC complexes and other associated molecules to naïve DCs. A variety of ex vivo and in vivo studies demonstrated that antigen-loaded dexosomes were able to initiate potent antitumor immunity. Human dexosomes can be easily prepared using monocyte-derived DCs isolated by leukapheresis of peripheral blood and treated ex vivo by cytokines and other factors. The feasibility of implementing dexosomes as therapeutic antitumor vaccines has been verified in two phase I and one phase II clinical trials in malignant melanoma and non small cell lung carcinoma patients. These studies proved the safety of dexosome administration and showed that dexosome vaccines have the capacity to trigger both the adaptive (T lymphocytes) and the innate (natural killer cells) immune cell recalls. In the current review, we will focus on the perspective of utilizing dexosome vaccines in the context of cancer immunotherapy. Keywords: Exosome, Dexosome, Dendritic cell-derived exosome, Extracellular vesicle, Anti-cancer vaccine, Immunotherapy
Background Dendritic cells (DCs) are adept antigen-presenting cells (APCs) of the mammalian immune system that function as the link between innate and adaptive immunity by recognizing, ingesting, processing, and presenting antigenic material to T lymphocytes, leading to either initiation or repression of immune responses [1]. The presentation of the antigenic material is conducted through the major histocompatibility complex (MHC) * Correspondence: [email protected]; [email protected] 3 School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Discovery Hall Room 182, 10900 University Blvd., VA 20110 Manassas, USA 2 Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, P.O. Box: 1138, Shafa St, Ershad Blvd., 57147 Urmia, Iran Full list of author information is available at the end of the article
class I and II molecules to naïve cytotoxic T lymphocytes (CTLs, CD8+ T cells) and naïve helper T cells (Ths, CD4+ T cells), respectively. DCs are a heterogeneous subpopulation of immune cells that are produced from precursor cells like monocytes in the bone marrow and are distributed among all organs and tissues via blood circulation. Upon antigen recogniti
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