Armed and targeted measles virus for chemovirotherapy of pancreatic cancer

Bossow, Sascha; Grossardt, Christian; Temme, Achim; Leber, Mathias F.; Sawall, Stefan; Rieber, Ernst Peter; Cattaneo, Roberto; Kalle, Christof von; Ungerechts, Guy

doi:10.1038/cgt.2011.30

Cited by 56 publications

(46 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More recent efforts used nonretroviral glycoproteins. A targeting system for replicating measles virus was developed by inserting ligand sequences into the C terminus of measles virus hemagglutinin (HA) H, a type II membrane protein (8,50). Once truncation of their cytoplasmic tails was shown to enable the use of measles virus H and fusion F proteins to pseudotype lentiviral vectors (19), the retargeting system was applied to lentiviral vectors, but the tendency of the chimeric scFv-H protein dimers to aggregate resulted in inconsistent expression and assembly into lentiviral particles (41).…”

mentioning

confidence: 99%

Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

Li¹,

Ryu

Krueger³

et al. 2012

J Virol

View full text Add to dashboard Cite

Here we report a novel viral glycoprotein created by replacing a natural receptor-binding sequence of the ecotropic Moloney murine leukemia virus envelope glycoprotein with the peptide ligand somatostatin. This new chimeric glycoprotein, which has been named the Sst receptor binding site (Sst-RBS), gives targeted transduction based on three criteria: (i) a gain of the use of a new entry receptor not used by any known virus; (ii) targeted entry at levels comparable to gene delivery by wild-type ecotropic Moloney murine leukemia virus and vesicular stomatitis virus (VSV) G glycoproteins; and (iii) a loss of the use of the natural ecotropic virus receptor. Retroviral vectors coated with Sst-RBS gained the ability to bind and transduce human 293 cells expressing somatostatin receptors. Their infection was specific to target somatostatin receptors, since a synthetic somatostatin peptide inhibited infection in a dose-dependent manner and the ability to transduce mouse cells bearing the natural ecotropic receptor was effectively lost. Importantly, vectors coated with the Sst-RBS glycoprotein gave targeted entry of up to 1 ؋ 10 6 transducing U/ml, a level comparable to that seen with infection of vectors coated with the parental wild-type ecotropic Moloney murine leukemia virus glycoprotein through the ecotropic receptor and approaching that of infection of VSV G-coated vectors through the VSV receptor. To our knowledge, this is the first example of a glycoprotein that gives targeted entry of retroviral vectors at levels comparable to the natural capacity of viral envelope glycoproteins.

show abstract

mentioning

confidence: 99%

Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

Li¹,

Ryu

Krueger³

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…In addition to making use of the immune system, bystander killing of non-infected tumor cells can also be increased by using virus-encoded prodrug convertases [112]. Upon infection of tumor cells, the transgene is expressed at the tumor site.…”

Section: Modes Of Action In Oncolytic Virotherapymentioning

confidence: 99%

Fighting Cancer with Mathematics and Viruses

Santiago¹,

Heidbuechel²,

Kandell³

et al. 2017

Preprint

View full text Add to dashboard Cite

After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude of novel agents and combination treatments are being evaluated for cancer therapy. Oncolytic agents preferentially replicate in tumor cells, inducing tumor cell lysis and complex anti-tumor effects, such as innate and adaptive immune responses and the destruction of tumor vasculature. With the availability of different vector platforms and the potential of both genetic engineering and combination regimens to enhance particular aspects of safety and efficacy, the identification of optimal treatments for patient subpopulations or even individual patients becomes a top priority. Mathematical modeling can provide support in this arena by making use of experimental and clinical data to generate hypotheses about the mechanisms underlying complex biology and, ultimately, predict optimal treatment protocols. Increasingly complex models can be applied to account for therapeutically relevant parameters such as components of the immune system. In this review, we describe current developments in oncolytic virotherapy and mathematical modeling to discuss the benefit of integrating different modeling approaches into biological and clinical experimentation. Conclusively, we propose a mutual combination of these fields of research for more efficient development and effective treatments.

show abstract

“…Measles viruses have also been shown to have oncolytic activity in pancreatic tumor xenografts in mice, and improve survival (38). Another type of measles virus, which was engineered to target prostate stem cell antigen (PSCA), a protein expressed in pancreatic cancer, has been shown to have beneficial effects particularly in gemcitabine resistant pancreatic adenocarcinoma (39). Reovirus, a virus whose replication is dependent on KRAS, a frequently found mutation in pancreatic cancer, has been shown to decrease tumor mass both locally and in the liver when administered intraperitoneally (40,41).…”

Section: Other Virusesmentioning

confidence: 99%

Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics

Yoo¹,

Kistler²,

Yan³

et al. 2016

J. Gastrointest. Oncol.

View full text Add to dashboard Cite

Endoscopic ultrasound (EUS) has become a mainstay in assisting in the diagnosis and staging of pancreatic cancer. In addition, EUS provides a modality to treat chronic pain through celiac plexus neurolysis. Currently, there is growing data and utilization of EUS in more diverse and innovative applications aimed at providing more sophisticated diagnostic, prognostic and therapeutic options for patients with pancreatic cancer. EUS delivery of chemotherapy, viral and biological vectors and fiducial markers may eventually revolutionize the way clinicians approach the care of a patient with pancreatic cancer. J Gastrointest Oncol 2016;7(6):1019-1029 jgo.amegroups.com pancreatic tumor, thus preventing side effects of systemic chemotherapy. It also allows for a more comprehensive realtime image, a shorter puncture pathway, and a lower risk of complications when compared to via computed tomography (CT) or abdominal ultrasound (US)-guided procedures.EUS-guided fine needle injections (EUS-FNIs) were initially studied in a porcine model where they injected paclitaxel into the pancreas; clinically detectable concentrations of the drug could not be detected beyond a distance of 30-50 mm from the injection site (6). Levy et al. studied EUS-FNI of gemcitabine in patients with unresectable cancer and demonstrated that several patients were able to be down staged and undergo subsequent resection (7). EUS-FNI of chemotherapy can be limited by the high density of fibrosis in pancreatic cancer, making it difficult to pierce the needle into the pancreatic tumor, and make it challenging to inject adequate amounts of an injected solution into the mass (7). Although interventional EUS has not been shown to significantly improve the survival rate and prolong the survival time in patients with pancreatic cancer, it can effectively induce tumor cell death. Additional studies are needed to further explore this therapeutic application in the future. EUS in predicting prognosis and response to chemotherapyIn addition to the potential for directly administering chemotherapy, assessing the prognosis and response to therapy is another developing role for EUS. Currently, many academic institutions and industry trials have adopted the response evaluation criteria in solid tumors (RECIST) criteria to help standardize the assessment of prognosis and response to therapies (8). RECIST criteria are largely based on radiographic cross-sectional imaging. It has been proposed that tumor response to neoadjuvant chemotherapy (defined by the RECIST criteria) would be required prior to surgery for borderline resectable pancreatic tumors. However, in a study by Katz et al. only 12% of cases had radiographic changes associated with neoadjuvant chemotherapy that met the RECIST criteria (9). Furthermore, only one patient out of 129 patients had enough of a reduction in tumor size to be reclassified as resectable via radiographic criteria, and yet 60% of those patients underwent surgical resection, suggesting that surgical resection in patients with bor...

show abstract

Armed and targeted measles virus for chemovirotherapy of pancreatic cancer

Cited by 56 publications

References 46 publications

Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

Fighting Cancer with Mathematics and Viruses

Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics

Contact Info

Product

Resources

About