Table I.
Current and past NIH registered clinical trials investigating EV-based therapeutics
| Disease Number of patients clinical trial (CT) phase | Source cell-type/application route | Isolation/purification | Modified/unmodified vesicle type | Results | Reference |
|---|---|---|---|---|---|
| Melanoma Stage III/IV, metastatic n=15 CT Phase I, open label |
Autologous monocyte-derived dendritic cell EVs. s.c. inj. | Ultrafiltration/UC sucrose cushion | MAGE3 loaded DC-EVs |
Proof of Feasibility & Safety; Toxicity<Grade II Maximum tolerated dose not reached,1 partial, 1 minor, 1 mixed response and 2 stable disease |
Escudier et al. (15) |
| Non-Small Cell Lung Cancer Stage IIIb, n=4 Stage IV, n=9 CT Phase I, open label |
Autologous monocyte-derived dendritic cell EVs. s.c. and intradermal inj. | Filtration/UC sucrose cushion | Peptide loaded | Feasibility & Safety; Toxicity<Grade I-II, 9/13 completed therapy, DTH against MAGE peptides in 3/9, specific T cell response in 1/3, NK lytic activity increased in 2/4 | Morse et al. (16) |
| Colon Cancer Stage III or IV n=40 CT Phase I, open label |
Autologous ascites-derived EVs (Aex) s.c. inj. | UC sucrose cushion | Unmodified±GM-CSF | Feasibility & Safety, Toxicity Grade I-II, TU-specific Cytotoxic T Cell Response in Aex+GM-CSF group (n=2) | Dai et al. (30) |
| Colon Cancer n=35 (estimated enrolment) CT Phase I, open label |
Plant nanovesicles not mentioned in NCT registry: route of application | Not mentioned | Curcumin, exogenous loading | NCT01294072 | |
| Type I Diabetes n=20 (estimated enrolment) CT Phase I, open label |
Umbilical cord blood (allogeneic) MSC-EVs not mentioned in NCT registry: route of application | Not mentioned | Unmodified | NCT02138331 | |
| Non-small cell lung cancer n=22 CT Phase II, open label |
Autologous IFN-γ matured monocyte-derived dendritic cell EVs intradermal inj. | Ultrafiltration/UC sucrose cushion | Peptide loaded | One patient exhibited a grade 3 hepatotoxicity. Seven patients (32%) experienced stabilization of >4 months: the primary endpoint (≥50% patients >4months) was not reached. No induction of T cell responses, but an increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. |
NCT01159288 Besse et al. (22) |
| Malignant Pleural Effusion n=30 (estimated enrolment) CT Phase II, open label |
Tumour cell–derived microparticles used as vectors for chemotherapeutic drugs pleural or peritoneal cavity. |
Not mentioned | Chemotherapeutic drugs, exogenous loading | NCT01854866 |
Aex, Ascites-derived exosomes; CT, clinical trials; DTH, delayed type hypersensitivity; DC, dendritic cells; GM-CSF, granulocyte-macrophage colony-stimulating factor; NIH, National Institute of Health; NK, natural killer; MAGE, melanoma antigen; s.c.inj, subcutaneous injection; TU, tumour.