Table 1.
MV Strain | Genetic Modification | Type of Cancer | Patients | Route of administration | Dose range and schedule | Combination treatment | Results/Current status |
---|---|---|---|---|---|---|---|
MV-Edm Zagreb vaccine strain (MV-EZ) | Commercially available measles vaccine (genetically unmodified) | CTLC | Five measles immune patients with ≥ stage IIb refractory or recurrent CTCL | Intratumoral | 102–103 TCID50 (each patient received a total of 2 or 4 injections) | Subcutaneous interferon-alpha administration 72 hours and 24 hours before viral treatment. | No dose-limiting toxicity. Complete regression of 1 injected lesion, partial regression of 4 treated lesions and no response of 1 injected lesion. Completed study [55]. |
MV-CEA (recombinant MV-Edm derivative) | Engineered to express the soluble extracellular domain of human CEA | Ovarian cancer | Twenty-one measles immune patients with recurrent ovarian cancer confined to the peritoneal cavity | Intraperitoneal | 103–109 TCID50 per dose (up to 6 monthly doses were administered per patient) | No | No dose-limiting toxicity. Dose-dependent CEA detection. Dose-dependent disease stabilization. Doubling of median overall survival compared with historical controls. Completed study [56]. |
MV-NIS (recombinant MV-Edm derivative) | Engineered to express NIS | Ovarian cancer | Sixteen measles immune patients with recurrent ovarian cancer confined to the peritoneal cavity | Intraperitoneal | 108–109 TCID50 per dose (up to 6 monthly doses were administered per patient) | No | No dose-limiting toxicity. Dose-dependent NIS-mediated radiotracer uptake. Dose-dependent disease stabilization. Doubling of median overall survival compared with historical controls. Completed study [59]. |
MV-NIS (recombinant MV-Edm derivative) | Engineered to express NIS | Ovarian cancer | Randomized phase II study of MV-NIS versus investigator’s choice chemotherapy accruing measles immune patients with platinum-resistant ovarian, fallopian, or peritoneal cancer | Intraperitoneal | 109 TCID50 per dose. Repeat every 28 days in the absence of disease progression or unacceptable toxicity. | No | Ongoing study (NCT02364713). |
MV-NIS (recombinant MV-Edm derivative) | Engineered to express NIS | Ovarian cancer | Accruing patients with recurrent ovarian cancer confined to the peritoneal cavity | Intraperitoneal | 109 TCID50 MV-NIS on day 1 cycle 1 ;MV-infected mesenchymal stem cells intraperitoneally on subsequent cycles every 28 days for up to 6 courses total, in the absence of disease progression or unacceptable toxicity. | MV-NIS infected mesenchymal stem cells | Ongoing study (NCT02068794). |
MV-CEA (recombinant MV-Edm derivative) | Engineered to express the soluble extracellular domain of human CEA | Glioblastoma multiforme | Accruing measles immune patients who are candidates for gross total or subtotal tumor resection. | Intracranial. | 105 to 2×107 TCID50 per dose (each patient will receive a single injection into the excised tumor cavity or 1 intratumoral dose (Group A) before surgery plus a second dose into the resection cavity) (Group B) | No | No dose-limiting toxicity to date. Ongoing study (NCT00390299). |
MV-NIS (recombinant MV-Edm derivative) | Engineered to express NIS | Multiple myeloma | Accruing patients with recurrent or refractory multiple myeloma | Intravenous | 106 to 109 TCID50 (1st patient cohort). MTD/100 to 81*MTD/100 (2nd patient cohort) | With or without cyclophosphamide pretreatment 48 hours before viral treatment | No dose-limiting toxicity to date. Preliminary report in 2 patients: M protein reduction and resolution of bone marrow plasmacytosis in both patients. Complete resolution ×9 months in all disease sites of 1 patient. Specificity, extend and duration of infection were monitored by NIS-mediated radiotracer uptake [63]. Ongoing study (NCT00450814). |
MV-NIS (recombinant MV-Edm derivative) | Engineered to express NIS | Multiple myeloma | Accruing measles-seronegative patients with recurrent or refractory multiple myeloma | Intravenous | Single dose of MV-NIS intravenously, initially +/− a 4-day course of cyclophosphamide. Currently single arm virus alone expansion study (109 TCID50 MV-NIS) in MV seronegative patients | 4-day course of cyclophosphamide | Ongoing study (NCT02192775). |
MV-NIS (recombinant MV-Edm derivative) | Engineered to express NIS | Mesothelioma | Accruing patients with malignant pleural mesothelioma | Intrapleural | 108 to 3 × 109 TCID50 per dose every 28 days (up to 6 monthly doses are allowed) | No | Ongoing study (NCT01503177). |
MV-NIS (recombinant MV-Edm derivative) | Engineered to express NIS | Squamous cell head and neck cancer or breast cancer | Accruing patients with recurrent or metastatic squamous cell carcinoma of the head and neck or breast cancer | Intratumorally | 108 to 109 TCID50 per dose. Single dose per patient administered intratumorally | No | Ongoing study (NCT01846091). |
MV-NIS (recombinant MV-Edm derivative) | Engineered to express NIS | Malignant Peripheral nerve sheath tumors | Accruing patients with malignant peripheral nerve sheath tumors | Intratumorally | 108 to 109 TCID50 per dose. Single dose per patient administered intratumorally | No | Ongoing study (NCT02700230) |
CEA: carcinoembryonic antigen; CTCL: Cutaneous T-cell lymphoma; MTD: Maximum tolerated dose; NIS: Sodium iodide symporter; TCID50: 50% tissue culture infective dose