Synergy between expression of fusogenic membrane proteins, chemotherapy and facultative virotherapy in colorectal cancer

Hoffmann, Dennis; Bangen, Jörg M.; Bayer, Wibke; Wildner, Oliver

doi:10.1038/sj.gt.3302806

Cited by 39 publications

(32 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…77 Since chemotherapy is effective in only a minority of glioblastoma patients, we evaluated whether the expression of FMG in glioblastoma cells in combination with temozolomide chemotherapy causes synergistic cell killing, as observed in two previous studies using colorectal and pancreatic cancer cells. 49,50 We qualitatively confirmed these studies in glioblastoma cells in vitro and in vivo. Despite the poor intratumoral transduction efficiency of the replication-defective vector Ad5/35.H/F we observed in the subcutaneous glioblastoma xenograft model in combination with temozolomide a significantly improved survival when compared to treatment with the individual compounds.…”

Section: Oncolytic Vectors For Gbm Treatment D Hoffmann and O Wildnersupporting

confidence: 71%

“…The replication-restricted oncolytic HSV-1 G47D 50 The helper-virus free HSV.H/F amplicon vector encoding measles virus fusogenic membrane proteins H and F under the transcriptional control of the tumor-specific human telomerase reverse transcriptase gene promoter (hTERT À548/ þ 5). 67 The vectors Ad5/35.H/F and HSV.H/F were generated and produced in the presence of the synthetic fusion inhibitory peptide Z-D-Phe-Phe-Gly-OH (10 mM; Bachem AG, Bubendorf, Switzerland).…”

Section: Viral Vectorsmentioning

confidence: 99%

“…49,50 Since glioblastoma are notoriously resistant to chemotherapy, we analyzed whether the expression of FMG in 66 was calculated based on the assumption that one plaque forming unit equals one biologically active virion. This provided the basis for the appropriate ratio of Ad5/35.H/F and temozolomide.…”

Section: Synergy Between Fmg Expression and Chemotherapy In Vitromentioning

confidence: 99%

“…To enhance the treatment efficacy of oncolytic vectors we combined viral oncolysis with the intratumoral expression of measles virus fusogenic membrane glycoproteins H and F (FMG) and temozolomide chemotherapy, since we demonstrated in previous studies in colorectal and pancreatic cancer cell lines that the expression of FMG synergistically enhances the cytotoxicity of clinically relevant chemotherapy and significantly improves therapeutic outcome in vivo. 49,50 In combination with oncolytic vectors this triple therapy, consisting of FMG expression, chemotherapy and viral oncolysis, had a significantly greater anti-neoplastic efficacy than treatment with its compounds as single or double agent therapy. 49,50 Since the FMG expression cassette exceeds the packaging capacity of replication-competent adenoviral vectors, 51 we trans-complemented the replication-defective adenovirus vector encoding the FMG with the conditionally replicative adenovirus Ad5/35.GD Á Ki.…”

Section: Introductionmentioning

confidence: 99%

“…49,50 In combination with oncolytic vectors this triple therapy, consisting of FMG expression, chemotherapy and viral oncolysis, had a significantly greater anti-neoplastic efficacy than treatment with its compounds as single or double agent therapy. 49,50 Since the FMG expression cassette exceeds the packaging capacity of replication-competent adenoviral vectors, 51 we trans-complemented the replication-defective adenovirus vector encoding the FMG with the conditionally replicative adenovirus Ad5/35.GD Á Ki. In cells transduced with both, the replication-defective vector encoding FMG and the replication-competent oncolytic vector, the replication-defective vector will be trans-complemented to allow vector amplification and intratumoral spread resulting in improved tumor transduction.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Comparison of herpes simplex virus- and conditionally replicative adenovirus-based vectors for glioblastoma treatment

Hoffmann

Wildner

2007

Cancer Gene Ther

Self Cite

View full text Add to dashboard Cite

In this study we compared side-by-side the anti-neoplastic activity of the oncolytic herpes simplex virus-1 (HSV-1) vector G47D with that of a conditionally replicative adenoviral vector for the treatment of glioblastoma. We analyzed the transduction efficiency of permanent glioblastoma cell lines and short-term cultures of glioblastoma cells with HSV.Luc and four adenovirus type 5 (Ad5)-based vectors that differed only in their fiber gene (Ad5.Luc, AdlucRGD, and the fiber chimeric vectors Ad5/3.Luc and Ad5/35.Luc). In the tested short-term cultures of glioblastoma cells the vectors Ad5/35.Luc and HSV.Luc had an equal transduction efficiency which was B70% higher than that of Ad5.Luc. In a subcutaneous xenograft glioblastoma model in nude mice we observed a significantly higher local tumor control with the G47D vector compared to the conditionally replicative Ad5/35 adenovirus. We confirmed in glioblastoma that the intratumoral expression of measles virus fusogenic membrane glycoproteins (FMG) encoded by replication-defective Ad5/35 or HSV-1 amplicon vectors synergistically enhances chemotherapy with temozolomide. The antineoplastic effect was superior when the replication-defective FMG encoding vectors were trans-complemented for replication with the respective oncolytic vector. This approach was necessary due to packaging constraints of adenovirus. At day 100, of 6 treated animals 1 was alive that received the Ad5/35-and 3 that received the HSV-1-based triple therapy. In an intracranial glioblastoma xenograft model we demonstrated the applicability of this strategy. Due to the higher oncolytic efficacy and packaging capacity of the HSV-1 vectors compared to adenovirus, these vectors are promising for the treatment of glioblastoma.

show abstract

Section: Oncolytic Vectors For Gbm Treatment D Hoffmann and O Wildnersupporting

confidence: 71%

Section: Viral Vectorsmentioning

confidence: 99%

Section: Synergy Between Fmg Expression and Chemotherapy In Vitromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comparison of herpes simplex virus- and conditionally replicative adenovirus-based vectors for glioblastoma treatment

Hoffmann

Wildner

2007

Cancer Gene Ther

Self Cite

View full text Add to dashboard Cite

show abstract

HSV as a Vector in Vaccine Development and Gene Therapy

Marconi

Argnani

Epstein

et al. 2009

Pharmaceutical Biotechnology

View full text Add to dashboard Cite

The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), major human pathogen whose lifestyle is based on a long-term dual interaction with the infected host characterized by the existence of lytic and latent infections, has allowed the development of potential vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous system, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases and targeted infection of specific tissues or organs. Three different classes of vectors can be derived from HSV-1: replication-competent attenuated vectors, replication-incompetent recombinant vectors and defective helper-dependent vectors known as amplicons. This chapter highlights the current knowledge concerning design, construction and recent applications, as well as the potential and current limitations of the three different classes of HSV-1-based vectors.

show abstract

Measles Virus for Cancer Therapy

Russell

Peng

Current Topics in Microbiology and Immunology

124

133

View full text Add to dashboard Cite

Measles virus offers an ideal platform from which to build a new generation of safe, effective oncolytic viruses. Occasional "spontaneous" tumor regressions have occurred during natural measles infections, but common tumors do not express SLAM, the wild-type MV receptor, and are therefore not susceptible to the virus. Serendipitously, attenuated vaccine strains of measles virus have adapted to use CD46, a regulator of complement activation that is expressed in higher abundance on human tumor cells than on their non transformed counterparts. For this reason, attenuated measles viruses are potent and selective oncolytic agents showing impressive antitumor activity in mouse xenograft models. The viruses can be engineered to enhance their tumor specificity, increase their antitumor potency and facilitate noninvasive in vivo monitoring of their spread. A major impediment to the successful deployment of oncolytic measles viruses as anticancer agents is the high prevalence of pre-existing anti measles immunity, which impedes bloodstream delivery and curtails intratumoral virus spread. It is hoped that these problems can be addressed by delivering the virus inside measles-infected cell carriers and/or by concomitant administration of immunosuppressive drugs. From a safety perspective, population immunity provides an excellent defense against measles spread from patient to carers and, in fifty years of human experience, reversion of attenuated measles to a wild type pathogenic phenotype has not been observed. Clinical trials testing oncolytic measles viruses as an experimental cancer therapy are currently underway.

show abstract

Synergy between expression of fusogenic membrane proteins, chemotherapy and facultative virotherapy in colorectal cancer

Cited by 39 publications

References 53 publications

Comparison of herpes simplex virus- and conditionally replicative adenovirus-based vectors for glioblastoma treatment

Comparison of herpes simplex virus- and conditionally replicative adenovirus-based vectors for glioblastoma treatment

HSV as a Vector in Vaccine Development and Gene Therapy

Measles Virus for Cancer Therapy

Contact Info

Product

Resources

About