Oncolytic virotherapy for human malignant mesothelioma: recent advances

Figures & data

Table 1 Completed and ongoing clinical trials of virotherapy for malignant mesothelioma treatment

Virus	Phase	Patients	Treatment modalities	Results	Reference
Adenovirus
Ad.HSVtk	I	21 MPM	No previous therapy Intrapleural injection (≥1.5×10^13 particles) + systemic ganciclovir	Well tolerated Antitumor antibodies 2 long-term survivors (>6.5 years)	^Citation55
Ad.hIFN-β (BG00001)	I	7 MPM 3 metastatic pleural effusions (ovary, lung, MPM)	No previous therapy Single intrapleural injection (9×10^11–3×10^12 particles)	Antitumor immune response in 7/10 patients Clinical response (SD) in 4/10 patients	^Citation35
Ad.hIFN-β (BG00001)	I	10 epithelioid MPM 7 metastatic pleural effusions (ovary, lung, breast)	2 intrapleural injections (7-day interval) (3×10^11–1×10^12 particles)	Well tolerated Antibody responses against tumor antigens 1 PR, 2 SD, 7 with survival >18 months	^Citation36
Ad.hIFN-α2b (SCH 721015)	Pilot	9 MPM	2 intrapleural injections (3-day interval) (3×10^11–1×10^12 particles)	Well tolerated Neutralizing antibodies 1 PR and 2 SD	^Citation34
Ad.hIFN-α2b (SCH 721015)	I/II	MPM	2 intrapleural injections + 4–6 cycles of chemotherapy	Ongoing	NCT01119664a
Ad.hIFN-α2b (SCH 721015)	I	MPM	2 intrapleural injections (3-day interval)	Ongoing	NCT01212367a
Ad5-D24-GMCSF	Unspecified	2 MPM	After chemotherapy Single intrapleural injection (2.5×10^11–3×10^11 particles)	Well tolerated Tumor-specific and virus-specific immunity 1 SD and 1 PD	^Citation54
Ad5/3-D24-GMCSF (ONCOS-102)	I	1 MPM	After chemo-/radiotherapy 4 intratumoral injections (3×10^11 particles) + cyclophosphamide (daily)	T CD8^+ tumor infiltration Th1 polarization	^Citation65
Poxvirus
VV-IL2		6 MPM	Intratumoral injection	Well tolerated No tumor regression	^Citation21
JX-594 (pexastimogene devacirepvec)	I	1 metastatic MPM	After chemotherapy Single intravenous injection (1.5×10^7 particles)	PR over 10 weeks	^Citation16
GL-ONC1	I	Malignant pleural effusions (primary, metastases, and MPM)	Intrapleural injection	Ongoing	NCT01766739a
Reovirus
Reolysin	I	1 MPM	Pretreatment with docetaxel Intravenous injection (1×10^9–3×10^10 TCID50) Up to 8 cycles (every 21 days) of 5 daily injections	Minor response 23% size decrease for 1 invaded lymph node	^Citation48
Measles virus
MV-NIS	I	MPM	Intrapleural injections Up to 6 cycles (every 28 days)	Ongoing	NCT01503177a
Herpesvirus
HSV-1716	I/IIa	MPM	Single/multiple intrapleural injections	Ongoing	NCT01721018a

Notes:

a NCT references can be viewed at https://clinicaltrials.gov/

Abbreviations: Ad, adenovirus; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL2, interleukin-2; MPM, malignant pleural mesothelioma; PD, progressive disease; PR, partial remission; SD, stable disease; VV, vaccinia virus; TCID, tissue culture infective dose.

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