Table 2.
Pre-clinical and clinical trials using exosomes for cancer therapy.
| Clinical Approach | Source of Exosomes | Clinical and Pre-Clinical Trial Features | Reference or Clinical Trials |
|---|---|---|---|
| Extracellular vesicles-based cancer vaccine | Dendritic cell | Combined Immunotherapy using metronomic cyclophosphamide followed by vaccination with tumor antigen-loaded dendritic cell-derived exosomes to inhibit Treg cell functions and restore T and NK cell effector functions while activating innate and adaptive immunity. | [107,108,109,110,111] NCT01159288 |
| T cell | A novel HER2 specific exosome/T-cell vaccine using polyclonal CD4+ T cells up taking exosomes released by HER2-specific dendritic cells may provide a new therapeutic alternative for patients with trastuzumab-resistant HER2+ breast cancer. | [112,113] | |
| Tumor cells | Prostate cancer cell-derived exosomes were used to prepare a vaccine anchoring an IFN-γ fusion protein on the surface of prostate cancer cell-derived exosomes, which retained its bioactivity and significantly inhibited tumor growth and prolonged the survival time of mice with prostate cancer. | [114] | |
| Tumor-associated or cell lines exosomes | Tumor cells | Exosomes secreted by diffuse large B cell lymphoma (DLBCL) induce apoptosis and upregulation of PD-1 in T cells. However, dendritic cells after being pulsed with DLBCL exosomes can stimulate T cells, increase IL-6 and TNFα expression and decrease the production IL-4 and IL-10. In another study, exosomes derived from heat-shocked mouse B lymphoma cells contained more HSP60 and HSP90, MHC I, MHC II, CD40, CD86, RANTES and IL-1β, which induce phenotypic and functional maturation of dendritic cells and activate CD8+ T cells to produce an antitumor effect | [115,116] |
| Natural killer cell-derived exosomes | NK cell markers such as NKG2D, CD94, perforin, granzymes and CD40L are expressed in NK-derived exosomes, along with other molecules involved in cytotoxicity, homing, cell adhesion and immune activation, suggesting that NK exosomes might be potentially exploited in support of cancer therapy. | [117,118] | |
| CAR-T cell/CTL-derived exosomes | CAR-T cells release exosomes that carry CAR and express a high level of cytotoxic molecules capable of inhibiting tumor growth. They do not express PD1 and have cytotoxic activity in vitro. The presence of CTL surface membrane molecules in CTL-derived exosomes ensures the unidirectional delivery of the lethal hit to targeted tumor cells. | [119,120] | |
| Mesenchymal stromal cells-derived exosomes | To determine the best dose and side effects of exosomes derived from mesenchymal stromal cells loaded with KrasG12D siRNA for the pancreatic cancer treatment. | NCT03608631 | |
| Genetically Engineered | Antibodies on exosomes | Synthetic multivalent antibodies retargeted exosomes (SMART-Exo) were genetically modified for displaying two distinct types of monoclonal antibodies on the exosome surface. They can simultaneously target tumor-associated human EGFR and T-cell surface CD3 receptor redirecting and activating T cells which exhibit a highly potent and specific antitumor activity against EGFR-expressing cancer cells. | [121,122] |
| Natural product | Therapeutic effect of plant exosomes | To determine the effect of exosome-delivered curcumin on immune modulation, cellular metabolism and phospholipid profile in normal colon tissue and colon tumors of newly diagnosed colon cancer patients who are undergoing surgery. To investigate the ability of plant (grape) exosomes to prevent oral mucositis associated with chemo-radiation treatment of head and neck cancer. Fruit-derived exosomes and curcumin should not generate any side-effects. | [123] NCT01294072, NCT01668849 |
| Chemical drugs | Exosome-based drug delivery platform for chemotherapeutic agents | Exosomes released by autologous macrophages loaded with paclitaxel (PTX) upon ultrasound treatment showed efficacy in the treatment of multidrug resistant cancer cells. This system may transport other chemotherapeutic agents in the future. | [103,104,124] |
| Purified exosomes from immature DCs (imDCs) loaded with doxorubicin (Dox) via electroporation, showed highly efficient targeting and Dox delivery to αv integrin-positive breast cancer cells | |||
| Therapeutic strategy of codelivering genes and chemotherapeutic drugs, A15-Exosomes coloaded with Doxorubicin and Cho-miR159 induced synergistic therapeutic effects in MDA-MB-231 cells by effectively silenced the TCF-7 gene improving anticancer effects, without adverse effects |
Legend: HER2, Erb-B2 Receptor Tyrosine Kinase 2; CD4, T-Cell Surface Glycoprotein CD4; HSP60, Heat Shock Protein 60; HSP90, Heat Shock Protein 90; MHC I, Class I Major Histocompatibility Complex; MHC II, Class II Major Histocompatibility Complex; CD40, CD40 Molecule; CD86, CD86 Molecule; RANTES, Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted; IL-1β, Interleukin 1 Beta; NKG2D, Receptor natural killer group 2, member D; CD90, CD90 molecule; CD40L, CD40 molecule ligand; CTL, Cytotoxic T cells; KRAS, KRAS Proto-Oncogene, GTPase; siRNA, small interfering RNA.