. 2019 Dec 5;32(2):113–120. doi: 10.4103/tcmj.tcmj_182_19

Table 2.

Summary of the exosome used in clinical trials with the complete reported results

Indication	Year, phase, patients	Source	Dose	Administration	Purification	Characterization	Bioactivity	Exosome manipulation	Results
Melanoma [35]	2000, Phase 1, (n=15)	imDC, autologous	4×10¹³ or 1.3 × 10¹³ MHC Class II molecules	SC (90% of the volume) and ID (10%) injections weekly for 4 weeks	500-kDa concentration and UC with D₂O/sucrose cushion	CD81 tetraspanin	SEE test of potency	Pulsed with MAGE 3 tumor peptides	No Grade II toxicity; No detected MAGE3-specific CD4+ and CD8+ T cells
Non-small cell lung cancer [25]	Not reported. Phase 1, (n=4)	imDCs, autologous	1.3×10¹³ MHC Class II molecules	SC (90% of the volume) and ID (10%) injections weekly for 4 weeks	500-kDa concentration and UC with D₂O/sucrose cushion	Not reported	MHC Class II molecules; ELISPOT for peptide-specific immune response	Pulsed with MAGE-A3, -A4, -A10, and MAGE-3DPO4 tumor peptide	Well-tolerated and only Grade 1-2 adverse events; MAGE-specific T-cell responses in 1/3 patients; increased NK lytic activity in 2/4 patients
Non-small cell lung cancer [26] [NCT01159288]	May 2010, Phase 2, (n=22)	Mature- dendritic (mDCs), autologous (induced by rIFN-γ)	8.5×10¹¹-1.0× 10¹³ MHC Class II molecules	Four ID at 1-week intervals	UF; DF and UC through a 1.21g/mL sucrose cushion	Exosome marker: Tetraspanin	Activation of LT11 cells Function: MHC class II molecules and CD40, CD86, and ICAM-1/CD54	Pulsed with MAGE-A1, -A3, NY-ESO-1, Melan-A/MART1, MAGE-A3-DP04, EBV tumor peptides	One patient had Grade 3 hepatotoxicity; boosting the NK cell arm of antitumor immunity
Colon cancer [27]	Not reported, Phase 1, (n=40)	Ascites, autologous	100-500 μg of protein	Four SC at weekly intervals	Differential centrifugation + sucrose/D₂O density gradient UC	Exosome marker: HSPs (including HSC70, HSP70, and HSP90), CD80, ICAM-1, CD71), and LAMP-3; EM	Function: Tumor-associated carcinoembryonic antigen, MHC-I, and MHC-II molecules	±GM-CSF	Safe, well-tolerated; tumor-specific antitumor CTL response in exosome plus GM-CSF group
Chronic kidney diseasesc [29]	April 2014, Phase 2/3, (n=40)	MSCs, allogeneic	100 μg/kg/dose	Two doses of MSC-EVs, intraarterial and intravenous injections	UC at 100,000 ×g	CD9, CD63; EM	CD45, CD73	Unmodified	Safe, well-tolerated; improved kidney function; decreased inflammation

UC: Ultracentrifugation, imDCs: Immature-dendritic cells, SC: Subcutaneous, ID: Intradermal, MSCs: Mesenchymal stem cells, UF: Ultrafiltration, DF: Diafiltration, EM: Electron microscopy, CTL: Cytotoxic T lymphocyte, GM-CSF: Granulocyte-macrophage colony-stimulating factor, NK: Natural killer, MHC: Major histocompatibility complex, ICAM-1: Intercellular adhesion molecule 1, LAMP-3: Lysosomal-associated membrane protein 3, HSP: Heat shock protein, rIFN-γ: Recombinant interferon-γ, EV: Extracellular vesicles