Sodium Iodide Symporter SPECT Imaging of a Patient Treated With Oncolytic Adenovirus Ad5/3-Δ24-hNIS

Rajecki, Maria; Kangasmäki, Aki; Laasonen, Leena; Escutenaire, Sophie; Hakkarainen, Tanja; Haukka, Jarmo; Ristimäki, Ari; Kairemo, Kalevi; Kangasniemi, Lotta; Kiljunen, Timo; Joensuu, Timo; Pesonen, Sari; Hemminki, Akseli

doi:10.1038/mt.2011.31

Cited by 21 publications

(23 citation statements)

References 16 publications

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“…Modest increases of CEA levels in the serum (12–16 ng/mL) were observed in all three patients treated at the highest dose level (10 9 TCID 50 ). Rajecki et al demonstrated the ability to perform sodium iodide symporter SPECT imaging in a patient treated with oncolytic adenovirus Ad5/3-Δ24-hNIS (40). …”

Section: Discussionmentioning

confidence: 99%

A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer

Kim

Dmitriev

O’Malley

et al. 2012

Clinical Cancer Research

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Purpose Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the MTD, toxicities, clinical efficacy and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Experimental Design Eligible patients were treated intraperitoneally (IP) for 3 days with 1×109 to 1×1012 vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed utilizing CTC Adverse Events grading and RECIST criteria. Imaging utilizing In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding and antibody response. Results Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade 1–2 constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients demonstrated stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies demonstrated presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts. Conclusions This study demonstrates the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted.

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Section: Discussionmentioning

confidence: 99%

A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer

Kim

Dmitriev

O’Malley

et al. 2012

Clinical Cancer Research

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“…To monitor viral replication in preclinical models, it has been cloned into measles virus [71,72], VSV [73], adenovirus [74,75], and vaccinia virus [76]. However, the replication of a second oncolytic adenovirus expressing the hNIS gene failed in a clinical setting [78]. In this study, viral replication was detected in seven of nine patients when 1 3 10 12 virus particles were injected.…”

Section: Nuclear Medicine-based Imagingmentioning

confidence: 81%

Imaging of Oncolytic Virus Gene Expression

Rojas

Thorne

2014

Gene Therapy of Cancer

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“…42 NIS has several advantages as a reporter gene because it is a self-protein; it is nonimmunogenic; it is nontoxic to the cells in which it is expressed; at 2 kb, the gene can be stably inserted into most viral vectors and NIS-compatible radioactive tracers such as 123 I and 99m TcO 4 are readily available for preclinical and clinical use in most medical centers. 20, 24, 25, 43 …”

Section: Discussionmentioning

confidence: 99%

“…NIS has been exploited as a marker gene for cancer gene therapy. 21, 22, 23, 24 Several oncolytic viruses have been equipped with a NIS gene to facilitate noninvasive in vivo monitoring 25, 26, 27, 28, 29, 30 and potency enhancement by adding I-131 ( 131 I). 20, 21, 23, 26, 30, 31 In this paper, we report a novel NIS-expressing oHSV whose viral dynamics are not altered by the NIS transgene.…”

Section: Introductionmentioning

confidence: 99%

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

Nakashima

Decklever

et al. 2013

Cancer Gene Ther

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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.

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Sodium Iodide Symporter SPECT Imaging of a Patient Treated With Oncolytic Adenovirus Ad5/3-Δ24-hNIS

Cited by 21 publications

References 16 publications

A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer

A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer

Imaging of Oncolytic Virus Gene Expression

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

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