HSV-NIS, an oncolytic herpes simplex virus type 1 encoding human sodium iodide symporter for preclinical prostate cancer radiovirotherapy

Abstract

Several clinical trials have shown that oncolytic herpes simplex virus type 1 (oHSV-1) can be safely administered to patients. However, virus replication in tumor tissue has generally not been monitored in these oHSV clinical trials, and the data suggest that its oncolytic potency needs to be improved. To facilitate noninvasive monitoring of the in vivo spread of an oHSV and to increase its antitumor efficacy, the gene coding for human sodium iodide symporter (NIS) was incorporated into a recombinant oHSV genome and the corresponding virus (oHSV-NIS) rescued in our laboratory. Our data demonstrate that a human prostate cancer cell line, LNCap, efficiently concentrates radioactive iodine after the cells have been infected in vitro or in vivo. In vivo replication of oHSV-NIS in tumors was noninvasively monitored by computed tomography/single-photon emission computed tomography imaging of the biodistribution of pertechnetate and was confirmed. LNCap xenografts in nude mice were eradicated by intratumoral administration of oHSV-NIS. Systemic administration of oHSV-NIS prolonged the survival of tumor-bearing mice, and the therapeutic effect was further enhanced by administration of 131I after the intratumoral spread of the virus had peaked. oHSV-NIS has the potential to substantially enhance the outcomes of standard therapy for patients with prostate cancer.

Oncolytic measles virus as a novel therapy for malignant peripheral nerve sheath tumors

“…In addition, the inclusion of NIS in the MV vector may enhance adjuvant radioablation therapy for the treatment of MPNST. It has been demonstrated previously that the selective uptake of radioactive iodine by NIS has antitumor activity (Li et al, 2012;Trujillo et al, 2012;Opyrchal et al, 2012;Li et al, 2013). The combined oncolytic properties of MV combined with radioablation could improve therapeutic outcomes for patients with both sporadic and NF1-associated MPNST tumors.…”

Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice

“…Systemic administration would be preferable in targeting advanced disease but has usually shown clearly limited efficacy (Berry et al , 2008; Li et al , 2013). Furthermore, preclinical oncolytic virotherapy research in prostate cancer has relied heavily on subcutaneous tumour models due to the high technical demands of orthotopic inoculation.…”

Viral Vector-Based Melanoma Gene Therapy

“…Adenovirus Ad5 dsDNA Strong immunogenicity Broad host range [37,38] Brain [39] Colon [40,41] Esophaegal [42] Gastric [43] Liver [44] Lung [45] Adeno associated viruses AAV (2,3,5,6,8,9) ssDNA Slow expression onset Chromosomal integration [46][47][48][49] Brain [50] Breast [51] Liver [52,53] Lung [54] Prostate [55] Retinoblastoma [56] Alphaviruses SFV, SIN ssRNA Broad host range low immunogenicity [32] Brain [57] Colon [58] Lung [59] Melanoma [60,61] Osteosarcoma [62] Pancreas [63] Prostate [64] Herpes simplex virus HSV1, HSV dsDNA Broad host range Latent infection [65,66] Brain [67,68] Colon [69] Prostate [70] Sarcoma [71] Skin [72] Reoviruses [76,79,80] Breast [81] Gastric ...…”