HSV-1 Viral Oncolysis and Molecular Imaging with PET

Kuruppu, Darshini; Dorfman, Jon D.; Tanabe, Kenneth K.

doi:10.2174/156800907780058871

Cited by 9 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3F). This property, which rests on the high specificity of the virus, could lead to the development of virus-mediated imaging of tumors, particularly since specific substrates of HSV thymidine kinase were designed, which enable the detection of HSV-infected cells by the non invasive, repeatable positron emission tomography (PET) [35].…”

Section: Discussionmentioning

confidence: 99%

Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus

et al. 2013

View full text Add to dashboard Cite

Oncolytic viruses aim to specifically kill tumor cells. A major challenge is the effective targeting of disseminated tumors in vivo. We retargeted herpes simplex virus (HSV) tropism to HER-2 oncoprotein p185, overexpressed in ovary and breast cancers. The HER-2-retargeted R-LM249 exclusively infects and kills tumor cells expressing high levels of human HER-2. Here, we assessed the efficacy of systemically i.p. delivered R-LM249 against disseminated tumors in mouse models that recapitulate tumor spread to the peritoneum in women. The human ovarian carcinoma SK-OV-3 cells implanted intraperitoneally (i.p.) in immunodeficient Rag2−/−;Il2rg−/− mice gave rise to a progressive peritoneal carcinomatosis which mimics the fatal condition in advanced human patients. I.p. administration of R-LM249 strongly inhibited carcinomatosis, resulting in 60% of mice free from peritoneal diffusion, and 95% reduction in the total weight of neoplastic nodules. Intraperitoneal metastases are a common outcome in breast cancer: i.p. administration of R-LM249 strongly inhibited the growth of ovarian metastases of HER-2+ MDA-MB-453 breast cells. Brain metastases were also reduced. Cumulatively, upon i.p. administration the HER-2-redirected oncolytic HSV effectively reduced the growth of ovarian and breast carcinoma disseminated to the peritoneal cavity.

show abstract

Section: Discussionmentioning

confidence: 99%

Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The destruction of cancer cells by replicating viruses or viral oncolysis is currently under investigation for cancer therapy 6 . This approach is based on lytic virus replication once it infects a cancer cell.…”

Section: Oncolytic Hsv-1 As a Therapeutic Option For Meningeal Metastmentioning

confidence: 99%

HSV-1 as a novel therapy for breast cancer meningeal metastases

Kuruppu

Tanabe

2015

Cancer Gene Ther

View full text Add to dashboard Cite

Meningeal metastasis is a fatal complication of breast cancer that affects 5–8 % of patients. When cancer cells seed in the meninges their subsequent growth results in severe neurological complications involving the cranial nerves, cerebrum and spinal cord, limiting life expectancy to less than 4 months. The incidences of meningeal metastases increase with prolonged life span resulting from treatment advances for primary breast cancer and their metastases. Currently there is no cure. Aggressive multimodal therapies such as radiation, chemotherapy (intra-CSF and systemic) are ineffective. Therapeutic agents are often quickly cleared from the CSF, while higher doses that can achieve a therapeutic response are highly toxic. The secure guarding of the subarachnoid space by the blood-brain-barrier on one side and the blood-CSF barrier on the other prevents chemotherapy from reaching the cancer cells in the meninges. These challenges with treating meningeal metastases highlight the urgent need for a new therapeutic modality. An ideal treatment would be an agent that avoids rapid clearance, remains within the CSF, reaches the meninges and selectively destroys tumor cells. Replication conditional oncolytic HSV-1 may be effective in this regard. Viral oncolysis, the destruction of cancer cells by replicating virus is under clinical investigation for cancers that are unresponsive to current therapies. It is based on the model of multiple cycles of lytic virus replication in cancer cells that amplify the injected dose. The therapeutic potential of oncolytic HSV-1 for breast cancer meningeal metastases is discussed here. HSV-1 could be a potential novel treatment for meningeal metastases that can be translated to the clinic.

show abstract

“…Most commonly ganciclovir is used as prodrug in this suicide gene therapy paradigm. Molecular imaging with PET using tk as a PET reporter gene offers the desired qualities of a noninvasive test which can be easily repeated to determine the location and magnitude of viral replication and tumour lysis and has been extensively used for both preclinical and clinical studies using HSV-1 oncolytic vectors [268]. Using replication-competent HSV-1 oncolytic virus with tk under the control of different promoters, it has been demonstrated that viral infection proliferation and promoter characteristics all interact to influence FIAU accumulation and imaging [269].…”

Section: Imaging Gene Therapymentioning

confidence: 99%

HSV Recombinant Vectors for Gene Therapy

Manservigi

Argnani²,

Marconi³

2010

TOVJ

View full text Add to dashboard Cite

The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), has allowed the development of potential replication-competent and replication-defective vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial. Replication-competent (oncolytic) vectors are becoming a suitable and powerful tool to eradicate brain tumours due to their ability to replicate and spread only within the tumour mass, and have reached phase II/III clinical trials in some cases. The progress in understanding the host immune response induced by the vector is also improving the use of HSV as a vaccine vector against both HSV infection and other pathogens. This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges.

show abstract

HSV-1 Viral Oncolysis and Molecular Imaging with PET

Cited by 9 publications

References 26 publications

Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus

Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus

HSV-1 as a novel therapy for breast cancer meningeal metastases

HSV Recombinant Vectors for Gene Therapy

Contact Info

Product

Resources

About