Newcastle disease virus selectively kills human tumor cells

Reichard, Kirk W.; Lorence, Robert M.; Cascino, Christopher J.; Peeples, Mark E.; Walter, Robert; Fernando, Michael B.; Reyes, Hernán M.; Greager, John A.

doi:10.1016/0022-4804(92)90310-v

Cited by 214 publications

(165 citation statements)

References 17 publications

Supporting

Mentioning

161

Contrasting

Unclassified

Order By: Relevance

“…The tumor-selective replication of naturally oncolytic viruses has been shown by several groups. 5,6,[38][39][40] It has been proposed for NDV that defects in the interferon pathway are a characteristic of tumor cells rendering these tumor cells vulnerable to virus replication. 41 Consistent with that hypothesis we see an initial infection with MTH87 and viral transgene expression in both nontransformed (HaCaT) cells and transformed (HT29) cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7] According to its pathogenicity in chicken, NDV is classified into lentogenic, mesogenic and velogenic strains. 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).…”

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

show abstract

“…Essentially specific pathways are required for the activation of replication cycle and due to extensive de-regulation of such pathways in cancer cells. These attempts to alter the viral tropism using pathway dependencies for viral replication have been utilized in the first generation of pre-clinical or clinically approved oncolytic viruses like Adenovirus (Ad): ONYX-015, dl922-947, Herpes Simplex Virus (HSV): G207, R3616, R1716, bM24-TE, Newcastle Disease Virus (NDV), Influenza Virus (IFA), Vesicular Stomatitis Virus (VSV) (Bischoff et al, 1996;O'Shea et al, 2004;Heise et al, 2000;Fueyo et al, 2000;Mineta et al, 1995;Cinatl et al, 2004;Reichard et al, 1992;Kuroda et al, 2006;Stojdl et al, 2003;Muster et al, 2004). The second approach for manipulating viral tropism and selective replication is to engineer viruses with genes responsible for replication controlled by tumor or tissue specific promoters.…”

Section: Gene Delivery -Viral and Non-viral Sytemsmentioning

confidence: 99%

“…VSV or NDV oncolytics are usually sensitive to interferon cytokines. However due to the attenuation of this antiviral response in host cells the viruses are able to replicate selectively in tumors (Stojdl et al, 2003;Noser et al, 2007;Lorence et al, 1988;Reichard et al, 1992). Activation of the Ras/MEK pathway in human cancers results in the inhibition of the protein kinase R (PKR) pathway.…”

Section: Gene Delivery -Viral and Non-viral Sytemsmentioning

confidence: 99%

Anticancer Gene Transfer for Cancer Gene Therapy

Pazarentzos

Mazarakis

2014

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by nonspecific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field.

show abstract

“…The plaque assay is considered as the "gold standard" for in vitro quantification of viral infectivity (8). Up to now, there are only two studies which reported the use of NDV plaque assay in human cancer cells (7,9). However, these studies used only the mesogenic NDV strains, and they did not discuss the details of the resulting plaque morphologies.…”

mentioning

confidence: 99%

Plaque formation by a velogenic Newcastle disease virus in human colorectal cancer cell lines

Chia¹,

Tan²,

Yusoff³

et al. 2012

View full text Add to dashboard Cite

. Abbreviations: NDV = Newcastle disease virus; CEF = chicken embryo fibroblasts; CRC = colorectal cancer Newcastle disease virus (NDV) was first reported to exhibit oncolytic activities on Ehrlich's ascites carcinoma in 1955 (1). Since then, various studies have also shown the effectiveness of NDV as an oncolytic agent (2). Thus far, only the lentogenic strains of NDV, such as HUJ (3), Ulster (4), and the mesogenic strains such as 73-T (5), MTH-68/H (6) and PV701 (7) were evaluated in clinical studies. To the best of our knowledge, no velogenic NDV strain has been tested in clinical trials hitherto. This might be due to its velogenic properties and to the specific regulations by the World Organization for Animal Health on the use of notifiable diseases. Nonetheless, in order to allow further investigation into the pathogenesis and oncolytic properties of this NDV strain, a proper quantitative method for its infectivity is needed.In the studies using the lentogenic and mesogenic strains, various techniques were used to measure the NDV infectivities and dosages, including the HAU (4) and EID 50 (5), as well as the plaque assay (7). The plaque assay is considered as the "gold standard" for in vitro quantification of viral infectivity (8). Up to now, there are only two studies which reported the use of NDV plaque assay in human cancer cells (7,9). However, these studies used only the mesogenic NDV strains, and they did not discuss the details of the resulting plaque morphologies. In view of the need for a standard quantitative method for velogenic NDV infectivity, we screened a panel of human colorectal cancer (CRC) cell lines to determine the best cell line to be used in a plaque assay. In this study, we used a method originally used to determine the PFU titer of respiratory syncytial virus (10), to determine the PFU titer of a velogenic NDV strain AF2240 (11).The cell lines and NDV used were examined for potential mycoplasma contamination. This was done to prevent any undesirable effects caused by the mycoplasmas. McKimmBreschkin (10) reported that cells contaminated with mycoplasmas produced a 10-fold lower efficiency of viral infection and replication. In addition, the shapes of the resulting plaques also became irregular. For plaque assay, each mycoplasma-free CRC cell line, namely SW620, SW480, DLD-1, Dks8, HCT116p53, and HT29 were seeded into 6-well plates (at approximately 2×10 6 cells per well) and incubated in a humidified 37°C incubator with 5% CO 2 . After rinsing twice with PBS, serial 10-fold dilutions of NDV stock virus in serum-free RPMI-1640 medium (PAA Laboratories) was added into appropriate wells and incubated for one hr with rocking at 15 min intervals. Following incubation, the viral suspensions were removed and the cells were rinsed twice with PBS. Pre-warmed serum-free media was used to dilute molten molecular biology grade of agarose (Vivantis), maintained at 42°C following sterilization at 121°C for 15 min at pressure of 15 psi, to a final concentration of 0.3% (w/v). The mixture (3 ml) w...

show abstract

Newcastle disease virus selectively kills human tumor cells

Cited by 214 publications

References 17 publications

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

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

Anticancer Gene Transfer for Cancer Gene Therapy

Plaque formation by a velogenic Newcastle disease virus in human colorectal cancer cell lines

Contact Info

Product

Resources

About