**6. TEX and cancer vaccine**

The use of exosomes in cancer treatment is made possible by the fact that exosomes can serve as delivery vehicles for genes and biological therapeutics. Tumor cells must be targeted explicitly while limiting adverse effects on healthy tissues to treat cancer effectively. Due to their ability to deliver their contents inside cancer cells, exosomes play a significant role in improving the therapeutic index of cancer treatment [68]. Exosomes exhibit these abilities because of the multivalent display of their surface fractions derived from cells, and it is impossible to recreate this complexity in synthetic nanoparticles [68]. Researchers have researched the development of therapeutic cancer vaccines, also known as active specific immunotherapy, and discovered that exosomes offer a great deal of promise for cancer immunotherapy and therapeutic cancer vaccines [69]. Exosomes from different cell types, such as immune cells, cancer cells, and normal cells, are compared for their effectiveness of exosome-based cancer immunotherapy. B cells secrete exosomes harboring MHC class II peptides that aid in antigen presentation to CD4+ T lymphocytes. Dendritic cell-derived exosomes (DEXs) play a critical role in anti-tumor immune response and may trigger a particular Cytotoxic T lymphocytes (CTLs) response and activate a T cell-dependent anti-tumor response [13].

TEXs, are modified for cancer vaccine development as they are a natural source of tumor antigens and can activate APCs to display them effectively [68]. Several studies have reported positive outcomes with TEX-based vaccination and observed activation of T-cell mediated antitumor immune reactions and tumor reduction [70, 71]. Researchers found that TEX immunization not only protected against tumor development and stimulated Th1 immune responses in melanoma animal models but also might limit lung metastasis [72]. In another study, immunization of syngeneic mice with exosomes generated by L1210 leukemia cells reduced tumor growth and provided resistance against subsequent tumor challenges [73]. In another study, both T lymphocyte proliferation and specific CTL activity were all stimulated when treated with HeLa cell-derived TEX [74]. Though many studies support the use of TEX-based vaccination, it is unlikely that TEXs alone can initiate acceptable levels of anti-tumor immunity due to their role in immunosuppression and the low immunogenicity of their components. Multiple strategies are devised to maximize antigen immunogenicity for effective tumor vaccination. TEXs might be modified by the following approaches (a) incorporating electroporated siRNA, (b) engineered to express tumor-associated and pathogenic antigens concomitantly, (c) tagging known immune boosters like CpG DNA and TLR ligands, (d) Direct fusion of TEXs with antigens, and (e) using external stimulus to increase TEX release [68, 75]. Innovative approaches are needed to make TEX-based cancer vaccines a reality.
