MTH-68/H Oncolytic Viral Treatment in Human High-Grade Gliomas

Csatary, Laszlo K.; Gosztonyi, Georg; Szeberényi, József; Fábián, Zsolt; Liszka, V; Bodey, B; Csatary, Christine M.

doi:10.1023/b:neon.0000021735.85511.05

Cited by 185 publications

(145 citation statements)

References 41 publications

Supporting

Mentioning

138

Contrasting

Unclassified

Order By: Relevance

“…The virulent strains also had a high capacity to lyse normal cells such as erythrocytes. This is particularly relevant because oncolytic NDV strains are already being used in clinical trials for systemic intravenous delivery (37)(38)(39). Although the oncolytic strains PV701 (37,38) (Wellstat Biologics Corporation, USA) or the Hungarian veterinary attenuated velogenic Herfordshire NDV fowl plaque vaccine (renamed MTH-68/H) (39), were found to be well tolerated when given i.v.…”

Section: Discussionmentioning

confidence: 99%

In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein

Bian

Wilden²,

Fournier³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

Abstract. The aim of the study was: i) to specifically target tumor tissue by Newcastle disease virus (NDV) with oncolytic properties, ii) to improve the delivery system for systemic application of NDV via a bispecific adapter protein and iii) to investigate anti-tumor activity and side-effects. We selected two oncolytic virus strains, one native and the other recombinant, which showed multicyclic replication patterns in tumor cells. In order to reduce normal cell binding, they were modified by preincubation with a recombinant bispecific protein which blocks the viral native cell binding site and introduces a new binding site for a tumor-associated target (in this study, the interleukin-2-receptor, IL-2R). After intravenous transfer to mice, uptake of modified NDV in liver, spleen, kidney and lung was greatly reduced in comparison to unmodified NDV as determined by RRT-PCR of viral M gene copies. In IL-2R + tumor bearing mice, the same assay revealed a high replication efficiency of the modified virus in the tumor tissue. Tumor therapy experiments showed that the side-effects induced by systemic application were greatly reduced by the adapter protein and that the anti-tumor effects were mostly undiminished. The demonstration of significant systemic anti-tumor activity of this viral vector suggests potential for augmentation by inclusion of one or more therapeutic genes.

show abstract

Section: Discussionmentioning

confidence: 99%

In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein

Bian

Wilden²,

Fournier³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Live attenuated strains of NDV have shown efficacy in mouse models of fibroblastoma (Lorence et al, 1994a), neuroblastoma (Lorence et al, 1994b;Reichard et al, 1993), colon (Schulze et al, 2009), prostate (Phuangsab et al, 2001), melanoma (Zamarin et al, 2009), large cell lung (Phuangsab et al, 2001) and breast carcinoma (Zhao et al, 2008;Janke et al, 2007). Moreover, live attenuated NDV strains MTH-68/H and PV701 are currently in clinical trials for high-grade gliomas (HGG) and advanced solid cancer, respectively (Csatary et al, 2004;Pecora et al, 2002).…”

Section: Newcastle Disease Virusmentioning

confidence: 99%

Herpes Simplex Type 1 for Use in Cancer Gene Therapy: Looking Backward to Move Forward

Cuddington¹,

Mossman²

2011

Viral Gene Therapy

View full text Add to dashboard Cite

“…8 The viruses that have been shown to selectively replicate in tumor cells and have antitumor activity in xenograft tumor model experiments belong to the mesogenic class (that is, pathogenic for chicken). To date two NDV strains have been used in patient tumor treatment, MTH68 with published case reports [9][10][11][12] and PV701 in clinical trials, the latter showing signs of efficacy. [13][14][15] A reverse genetic system to engineer the NDV genome was first described for the lentogenic (vaccine) strains LaSota by Peeters et al 16 and Clone 30 by Rö merOberdö rfer et al, 17 and later the strain Hitchner B1.…”

Section: Introductionmentioning

confidence: 99%

Generation of a recombinant oncolytic Newcastle disease virus and expression of a full IgG antibody from two transgenes

et al. 2008

View full text Add to dashboard Cite

The most advanced oncolytic Newcastle disease virus (NDV) strains that are used in clinical trials for the treatment of cancer are wild-type mesogenic strains. These virus strains have an inherent, nongenetically engineered, oncolytic activity and selectively replicate in tumor cells but not in normal human cells. To date no investigations have been performed with genetically engineered mesogenic NDV regarding the oncolytic activity. We describe here the generation of recombinant viruses of the mesogenic naturally oncolytic NDV strain MTH68. We show that not only one, but also two additional transgenes coding for amino-acid chains with a molecular weight of 25 and 50 kDa can be inserted into the viral genome without affecting viral growth, oncolytic potency or tumor-selective replication of the virus. Transgenic expression of the heavy and light chains of a monoclonal antibody, as separate additional transcriptional cassettes, leads to the expression of full immunoglobulin G (IgG) monoclonal antibody by recombinant NDV. Infection of tumor cells with antibody-transgenic viruses results in the efficient production and secretion of a functional full size IgG antibody by the tumor cells, that specifically binds to its target-antigen in tumor tissue. This approach will allow to combine the advantages of oncolytic RNA viruses and monoclonal antibodies in a single powerful anticancer agent with improved or even new therapeutic properties.

show abstract

MTH-68/H Oncolytic Viral Treatment in Human High-Grade Gliomas

Cited by 185 publications

References 41 publications

In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein

In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein

Herpes Simplex Type 1 for Use in Cancer Gene Therapy: Looking Backward to Move Forward

Generation of a recombinant oncolytic Newcastle disease virus and expression of a full IgG antibody from two transgenes

Contact Info

Product

Resources

About