Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy

Abstract

MV-NIS is an engineered measles virus that is selectively destructive to myeloma plasma cells and can be monitored by noninvasive radioiodine imaging of NIS gene expression. Two measles-seronegative patients with relapsing drug-refractory myeloma and multiple glucose-avid plasmacytomas were treated by intravenous infusion of 1011 TCID50 (50% tissue culture infectious dose) infectious units of MV-NIS. Both patients responded to therapy with M protein reduction and resolution of bone marrow plasmacytosis. Further, one patient experienced durable complete remission at all disease sites. Tumor targeting was clearly documented by NIS-mediated radioiodine uptake in virus-infected plasmacytomas. Toxicities resolved within the first week after therapy. Oncolytic viruses offer a promising new modality for the targeted infection and destruction of disseminated cancer.

Trial Watch—Oncolytic viruses and cancer therapy

“…in combination with cisplatin-based chemoradiation 188,189 (NCT01584284). 190 Moreover, (1) G207 (a conditionally replicating HSV-1 strain) 191 has been tested in combination with radiation therapy in nine patients with progressive, recurrent glioblastoma (NCT00157703); 192 (2) the therapeutic profile of NTX-010 (a native, replication-competent variant of the Seneca Valley picornavirus, also known as SVV-001) 193 in combination with metronomic cyclophosphamide has been assessed in 22 children with neuroendocrine tumors (NCT01048892); 194 (3) Ad5-yCD/mutTKSR39rep-ADP (a replication competent adenoviral strain endowed with superior oncolytic potential) 195 has been tested in combination with intensity modulated radiation therapy 196,197 in 44 prostate carcinoma patients; 198 (4) the clinical activity of HF10 (a replicative HSV-1 strain) 199 has been investigated in 17 subjects with advanced malignancies, who received HF10 intratumorally as standalone immunotherapeutic intervention; 200 (5) MV-NIS (a strain of oncolytic measles virus encoding the human thyroidal sodium iodide symporter), 201,202 has been tested as standalone immunotherapeutic intervention in two myeloma patients; 203 (6) the safety and efficacy of OBP-301 (an oncolytic adenovirus engineered to selectively target telomerase reverse transcriptase (TERT)-overexpressing cells, also known as telomelysin) 204 has been assessed in six elderly subjects with esophageal carcinoma, who received OBP-301 i.t. in combination with radiation therapy (UMIN000010158); 205 and (7) the clinical profile of an oncolytic variant Western Reserve vaccinia virus artificially endowed with improved specificity 206 has been evaluated in 16 individuals with advanced solid malignancies, who were treated with oncolytic virothapy i.t.…”

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

“…The therapeutic concept takes advantage of both the specificity of the virus for tumor cells and of the lytic nature of a measles virus infection. Derivatives of measles virus vaccine strains are currently undergoing clinical testing for their efficacy in oncolytic virotherapy [42]. However, the broad application of measles virus in cancer therapy can only be successful if high titers of pure infectious virus particles can be manufactured.…”

“…However, the broad application of measles virus in cancer therapy can only be successful if high titers of pure infectious virus particles can be manufactured. As discussed above for gene therapy vectors, oncolytic measles virus doses of 10 9 -10 12 particles are required per person and application [42].…”

Oncolytic viruses: From bench to bedside with a focus on safety

“…70 Completed and ongoing clinical trials in patients with T cell lymphoma, ovarian cancer or glioblastoma multiforme have first used wild type MeV and later recombinant MeV expressing marker genes CEA and NIS. [72][73][74] Intratumoral, intraperitoneal and intravenous administration have been reported using doses up to 10 9 infectious viral particles without dose limiting toxicity or MeV induced immunosuppression. [72][73][74] Although wildtype MeV can cause potentially serious disease, attenuated MeV vaccine strains like Edmonston have an excellent safety record.…”

“…[72][73][74] Intratumoral, intraperitoneal and intravenous administration have been reported using doses up to 10 9 infectious viral particles without dose limiting toxicity or MeV induced immunosuppression. [72][73][74] Although wildtype MeV can cause potentially serious disease, attenuated MeV vaccine strains like Edmonston have an excellent safety record. 69 In clinical trials with rMeV-CEA, no evidence was seen of shedding in sputum and urine samples of patients who were intraperitoneally injected.…”