Induction of Tumors in Hamsters with an Avian Adenovirus (CELO)

Sarma, Padman S.; Huebner, Robert J.; Lane, William T.

doi:10.1126/science.149.3688.1108

Cited by 75 publications

(27 citation statements)

References 11 publications

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“…Thus type 2 (GAL) failed to produce tumours in hamsters (Sarma et al, 1965) and more recent work (Fadly et al, 1976) using a type 1 (Indiana C) a type 5 (Tipton) and an unclassified virus (DPl-2) failed to produce tumours. It is especially interesting that the Indiana C isolate was not oncogenic as it is in the same serological group as the Phelps isolate which is oncogenic.…”

Section: Oncogenicity Of Fowl Adenovirusesmentioning

confidence: 88%

“…Initially only a well differentiated fibrosarcoma at the site of inoculation was reported (Sarma et al, 1965), but subsequently hepatomas (Anderson et al, 1971a), ependymonas (Mancini et al, 1969), adenocarcinomas and hepatomas (Stenback et al, 1973) and other types of sarcoma (Jones et al, 1970) have been described. In vitro transformation of human and hamster cells have also been reported (Anderson et al, 1969a and b).…”

Section: Oncogenicity Of Fowl Adenovirusesmentioning

confidence: 99%

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Avian adenoviruses ‐ a review

1977

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Section: Oncogenicity Of Fowl Adenovirusesmentioning

confidence: 88%

Section: Oncogenicity Of Fowl Adenovirusesmentioning

confidence: 99%

Avian adenoviruses ‐ a review

1977

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“…8,9 In addition, the feasibility of deleting the long fiber from the CELO genome was demonstrated, providing an opportunity for implementation of ''retargeting'' strategies to CELO vectors. 26 Although wt CELO virus was shown to induce tumors in newborn hamsters, 55 this does not directly indicate that wt CELO is carcinogenic for humans since it was not shown to cause cancer in immunocompetent animal models. With respect to the safety of CELO-TK, this vector expresses the prodrug-activating enzyme HSV-tk, a safety strategy often employed in gene therapy vectors.…”

Section: Discussionmentioning

confidence: 99%

Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

et al. 2005

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Avian adenovirus CELO is a novel adenovirus vector system with the advantages of efficient production, high virion stability, and the absence of crossreactivity with Ad5-neutralizing antibodies. In this study, we evaluated the anticancer efficacy of a CELO vector encoding the herpes simplex virus type 1 thymidine kinase, a prodrug-activating therapeutic gene. Vectors carrying the gene for HSV-tk or EGFP under the control of the HCMV promoter in place of the ''nonessential'' region of the CELO genome were constructed. Anticancer activity of the CELO-TK vector was studied in vitro, in human and murine tumor cells in cell culture, and in vivo, in established subcutaneous murine B16 melanoma tumors in C57BL/6 mice. The CELO-TK vector mediated delivery of functional HSV-tk to tumor cell lines in cell culture. Comparison of the CELO-TK vector to a first-generation human adenovirus type 5 vector Ad5-TK in cultured H1299 cells showed equal levels of functional activity at increasing multiplicities of infection with CELO-based vector. CELO vectors allowed for transduction and expression of EGFP and HSV-tk genes in subcutaneous melanoma tumors in C57BL/6 mice. Intratumoral injections of CELO-TK followed by ganciclovir administration resulted in suppression of tumor growth and significantly increased the median of survival. The results of the study demonstrated the efficacy of CELO vector as a vehicle for the delivery of prodrug-activating genes such as HSV-tk to tumor cells in vitro and in vivo. Cancer Gene Therapy ( 1 This experimental approach to cancer treatment is currently in a transition from promise to reality with recent approval of an adenovirus (Ad) vector expressing p53 for use in clinics and with many more vectors in late stages of clinical trials.2 At the same time, new generations of cancer gene therapy vectors are being developed that will provide higher levels of efficacy, specificity, and cost-effectiveness.Whereas human Ad type 5 (Ad5) is a common platform for Ad vectors for the in vitro and in vivo delivery of genes, 3,4 non-human adenoviruses (Ads), also referred to as ''xenogeneic'' vectors, are currently emerging as alternative or additional gene delivery vehicles. 5,6 Avian Ad CELO (FAV-1) is a novel non-human Ad vector that has potential advantages for the development of anticancer vectors including: (i) the absence of pre-existing immunity to CELO in the human population, 7 (ii) the absence of immunological crossreactivity between virions of Ad5 and CELO, 8 which allows for in vivo transduction by CELO vectors in the presence of anti-Ad5 neutralizing antibodies, 9 (iii) higher stability of CELO virions as compared to Ad5 virions, 7 (iv) the natural inability of CELO to replicate in non-avian cells, which renders CELO vectors gene delivery vehicles rather than replicative agents in mammalian cells, 7 (v) the ability of CELO vectors to grow in noncomplementing cells resulting in the absence of recombination with the homologous viral DNA sequences in the genome of a complementing cell line, and the a...

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“…More recently CELO virus has been isolated in England from eggs laid by an apparently normal flock with exceptionally high egg production (Cook, 1968). Sarma, Huebner & Lane (1965) have described the induction of fibrosarcomas in hamsters inoculated with CELO virus when newborn and the oncogenic properties of the virus have been confirmed in this laboratory with two different strains of CELO virus (Schild, Oxford & Potter, to be published). CELO virus is a potential contaminant of egg-prepared vaccines and because of its stability (Petek, Feliuga & Zoletto, 1963) may survive vaccine virus inactivation procedures.…”

Section: Introductionmentioning

confidence: 93%

Chick embryo lethal orphan (CELO) virus as a possible contaminant of egg-grown virus vaccines

Oxford

Potter

1969

J. Hyg.

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SUMMARYThe inactivation kinetics of CELO virus were studied in the presence of 1/4000 formaldehyde. Inactivation of the virus by formaldehyde at 4° C. was not complete after 14 days incubation. Formaldehyde inactivation at 36° C., however, was rapid and no virus was detected after 24 hr. incubation.Neutralizing antibody to CELO virus was detected in 20–88% of sera tested from five flocks of hens. This suggested dissemination of the virus in England and Scotland. However, no CELO virus neutralizing antibody at a serum dilution of 1/8 was detected in 142 normal human sera or in 229 sera from persons who had been immunized with egg grown, inactivated influenza virus vaccine.We would like to thank Professor C. H. Stuart-Harris and Drs J. E. Wilson, D. A. Martin and D. Breeze for their help and their criticisms of the manuscript.Dr G. C. Schild kindly supplied a number of the human sera used in the study. The study was financed in part by the National Fund for Research in Poliomyelitis and other Crippling Diseases and by the British Empire Cancer Campaign.

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Induction of Tumors in Hamsters with an Avian Adenovirus (CELO)

Cited by 75 publications

References 11 publications

Avian adenoviruses ‐ a review

Avian adenoviruses ‐ a review

Avian adenovirus vector CELO-TK displays anticancer activity in human cancer cells and suppresses established murine melanoma tumors

Chick embryo lethal orphan (CELO) virus as a possible contaminant of egg-grown virus vaccines

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