Table 2.

Summary of clinical trials that assessed or are evaluating the application of EVs in anticancer therapy.

Cancer type	Phase of study	State	Purpose of clinical trials and outcome	References
Non-small-cell lung carcinoma (NSCLC)	Phase I	USA	The study intended to use exosomes carrying specific antigens to activate immune response against established tumours. Exosomes from dendritic cells (DCs) obtained through leukophoresis were collected from patients with advanced NSCLC with tumor expression of MAGE-A3 or -A4 antigens. These exosomes, loaded with specific MAGE peptides, were administrated to patients to induce immune response. This form of immunotherapy was well tolerated; in 3 of 9 patients, who had no reactivity to MAGE before immunization, an increased systemic immune response against MAGE, an increased NK cells lytic activity, and a long term stabilization of disease in some patients were observed.	[126]
Melanoma	Phase I	France	The study was intended to asses a DCs-derived exosomes based vaccination in melanoma patients; autologous exosomes pulsed with MAGE 3 peptides were used to induce the immunization in patients with melanoma at stages III and IV. The study confirmed the feasibility of exosomes production in large scale, the safety of their administration to patients, and the good tolerance in cancer patients; nevertheless, even if treatment induced minor or partial responses in some patients, no MAGE3 specific T-cell immune responses were detected in peripheral blood of the same patients.	[127]
Colorectal cancer	Phase I	China	The study wanted to assess the possibility to use exosomes in immunotherapy and reported that exosomes derived from ascites, if subcutaneously administrated with GM-CFS (granulocyte macrophage colony-stimulating factor) in patients with colorectal cancer, were able to induce an antigen-specific anticancer cytotoxic T lymphocyte response. Toxicity of exosomes was minimal and patients tolerated very well the administration.	[128]
NSCLC	Ongoing phase II	France	The study aims to assess the efficacy of a therapeutic vaccine constituted by autologous DC-derived exosomes in nonoperable and advanced NSCLC patients (stages IIIB and IV), to verify if they are able to stimulate the patients' natural defenses in order to obtain the stop of tumor progression or tumor regression.	[129]