| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Departments of Radiation Oncology and Molecular Biology, Henry Ford Health System, Detroit, Michigan 48202 [K. R. R., S. O. F., K. Z., J. D. G., D. L. P., J. H. K.], and ONYX Pharmaceuticals, Richmond, California 94806 [C. C. H., D. H. K.]
The E1B-deleted, replication-competent ONYX-015 (dl1520) adenovirus was originally described as being able to selectively kill p53-deficient cells due to a requirement of p53 inactivation for efficient viral replication. This hypothesis has become controversial because subsequent in vitro studies have demonstrated that the host range specificity of ONYX-015 is independent of p53 gene status. Using a pair of isogenic cell lines that differ only in their p53 status, we demonstrate here that although ONYX-015 can replicate in both p53 wild-type and mutant cells in vitro, the virus demonstrates significantly greater antitumor activity against mutant p53 tumors in vivo. Moreover, ONYX-015 viral therapy can be combined with radiation to improve tumor control beyond that of either monotherapy. The results demonstrate that ONYX-015 can discern in vivo between tumors having a different p53 status and that it may be an effective neoadjuvant to radiation therapy.
This article has been cited by other articles:
|
|
 |
|
  X. Zheng, X.-M. Rao, J. G. Gomez-Gutierrez, H. Hao, K. M. McMasters, and H. S. Zhou Adenovirus E1B55K Region Is Required To Enhance Cyclin E Expression for Efficient Viral DNA Replication J. Virol., April 1, 2008; 82(7): 3415 - 3427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Egami, K. Ohuchida, K. Mizumoto, M. Onimaru, H. Toma, S. Nishio, E. Nagai, K. Matsumoto, T. Nakamura, and M. Tanaka Radiation Enhances Adenoviral Gene Therapy in Pancreatic Cancer via Activation of Cytomegalovirus Promoter and Increased Adenovirus Uptake Clin. Cancer Res., March 15, 2008; 14(6): 1859 - 1867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L.M. Lamfers, S. Idema, L. Bosscher, S. Heukelom, S. Moeniralm, I. H. van der Meulen-Muileman, R. M. Overmeer, P. van der Valk, V. W. van Beusechem, W. R. Gerritsen, et al. Differential Effects of Combined Ad5-{Delta}24RGD and Radiation Therapy in In vitro versus In vivo Models of Malignant Glioma Clin. Cancer Res., December 15, 2007; 13(24): 7451 - 7458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Chu, D. E. Post, F. R. Khuri, and E. G. Van Meir Use of Replicating Oncolytic Adenoviruses in Combination Therapy for Cancer Clin. Cancer Res., August 15, 2004; 10(16): 5299 - 5312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gomez-Manzano, W.K. A. Yung, R. Alemany, and J. Fueyo Genetically modified adenoviruses against gliomas: From bench to bedside Neurology, August 10, 2004; 63(3): 418 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. O. Freytag, H. Stricker, J. Pegg, D. Paielli, D. G. Pradhan, J. Peabody, M. DePeralta-Venturina, X. Xia, S. Brown, M. Lu, et al. Phase I Study of Replication-Competent Adenovirus-Mediated Double-Suicide Gene Therapy in Combination with Conventional-Dose Three-Dimensional Conformal Radiation Therapy for the Treatment of Newly Diagnosed, Intermediate- to High-Risk Prostate Cancer Cancer Res., November 1, 2003; 63(21): 7497 - 7506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Stubdal, N. Perin, M. Lemmon, P. Holman, M. Bauzon, P. M. Potter, M. K. Danks, A. Fattaey, T. Dubensky, and L. Johnson A Prodrug Strategy Using ONYX-015-Based Replicating Adenoviruses to Deliver Rabbit Carboxylesterase to Tumor Cells for Conversion of CPT-11 to SN-38 Cancer Res., October 15, 2003; 63(20): 6900 - 6908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Portella, R. Pacelli, S. Libertini, L. Cella, G. Vecchio, M. Salvatore, and A. Fusco ONYX-015 Enhances Radiation-Induced Death of Human Anaplastic Thyroid Carcinoma Cells J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 5027 - 5032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Wein, J. T. Wu, and D. H. Kirn Validation and Analysis of a Mathematical Model of a Replication-competent Oncolytic Virus for Cancer Treatment: Implications for Virus Design and Delivery Cancer Res., March 15, 2003; 63(6): 1317 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Hecht, R. Bedford, J. L. Abbruzzese, S. Lahoti, T. R. Reid, R. M. Soetikno, D. H. Kirn, and S. M. Freeman A Phase I/II Trial of Intratumoral Endoscopic Ultrasound Injection of ONYX-015 with Intravenous Gemcitabine in Unresectable Pancreatic Carcinoma Clin. Cancer Res., February 1, 2003; 9(2): 555 - 561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Makower, A. Rozenblit, H. Kaufman, M. Edelman, M. E. Lane, J. Zwiebel, H. Haynes, and S. Wadler Phase II Clinical Trial of Intralesional Administration of the Oncolytic Adenovirus ONYX-015 in Patients with Hepatobiliary Tumors with Correlative p53 Studies Clin. Cancer Res., February 1, 2003; 9(2): 693 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wadler, B. Yu, J.-Y. Tan, R. Kaleya, A. Rozenblit, D. Makower, M. Edelman, M. Lane, E. Hyjek, and M. Horwitz Persistent Replication of the Modified Chimeric Adenovirus ONYX-015 in both Tumor and Stromal Cells from a Patient with Gall Bladder Carcinoma Implants Clin. Cancer Res., January 1, 2003; 9(1): 33 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Reid, E. Galanis, J. Abbruzzese, D. Sze, L. M. Wein, J. Andrews, B. Randlev, C. Heise, M. Uprichard, M. Hatfield, et al. Hepatic Arterial Infusion of a Replication-selective Oncolytic Adenovirus (dl1520): Phase II Viral, Immunologic, and Clinical Endpoints Cancer Res., November 1, 2002; 62(21): 6070 - 6079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Suzuki, R. Alemany, M. Yamamoto, and D. T. Curiel The Presence of the Adenovirus E3 Region Improves the Oncolytic Potency of Conditionally Replicative Adenoviruses Clin. Cancer Res., November 1, 2002; 8(11): 3348 - 3359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. M. Lamfers, J. Grill, C. M. F. Dirven, V. W. van Beusechem, B. Geoerger, J. van den Berg, R. Alemany, J. Fueyo, D. T. Curiel, G. Vassal, et al. Potential of the Conditionally Replicative Adenovirus Ad5-{Delta}24RGD in the Treatment of Malignant Gliomas and Its Enhanced Effect with Radiotherapy Cancer Res., October 15, 2002; 62(20): 5736 - 5742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. O. Freytag, M. Khil, H. Stricker, J. Peabody, M. Menon, M. DePeralta-Venturina, D. Nafziger, J. Pegg, D. Paielli, S. Brown, et al. Phase I Study of Replication-competent Adenovirus-mediated Double Suicide Gene Therapy for the Treatment of Locally Recurrent Prostate Cancer Cancer Res., September 1, 2002; 62(17): 4968 - 4976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Mullen and K. K. Tanabe Viral Oncolysis Oncologist, April 1, 2002; 7(2): 106 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. A. Ring Cytolytic viruses as potential anti-cancer agents J. Gen. Virol., March 1, 2002; 83(3): 491 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Geoerger, J. Grill, P. Opolon, J. Morizet, G. Aubert, M.-J. Terrier-Lacombe, B. Bressac de-Paillerets, M. Barrois, J. Feunteun, D. H. Kirn, et al. Oncolytic Activity of the E1B-55 kDa-deleted Adenovirus ONYX-015 Is Independent of Cellular p53 Status in Human Malignant Glioma Xenografts Cancer Res., February 1, 2002; 62(3): 764 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Li, K. Dower, Y. Ma, Y. Tian, and T. L. Benjamin A tumor host range selection procedure identifies p150sal2 as a target of polyoma virus large T antigen PNAS, December 4, 2001; 98(25): 14619 - 14624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. DeWeese, H. van der Poel, S. Li, B. Mikhak, R. Drew, M. Goemann, U. Hamper, R. DeJong, N. Detorie, R. Rodriguez, et al. A Phase I Trial of CV706, a Replication-competent, PSA Selective Oncolytic Adenovirus, for the Treatment of Locally Recurrent Prostate Cancer following Radiation Therapy Cancer Res., October 1, 2001; 61(20): 7464 - 7472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Koch, J. Gatfield, C. Lober, U. Hobom, C. Lenz-Stoppler, J. Roth, and M. Dobbelstein Efficient Replication of Adenovirus Despite the Overexpression of Active and Nondegradable p53 Cancer Res., August 1, 2001; 61(15): 5941 - 5947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, T. DeWeese, J. Dilley, Y. Zhang, Y. Li, N. Ramesh, J. Lee, R. Pennathur-Das, J. Radzyminski, J. Wypych, et al. CV706, a Prostate Cancer-specific Adenovirus Variant, in Combination with Radiotherapy Produces Synergistic Antitumor Efficacy without Increasing Toxicity Cancer Res., July 1, 2001; 61(14): 5453 - 5460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Wilcox, W. Yang, D. Senger, N. B. Rewcastle, D. G. Morris, P. M. A. Brasher, Z. Q. Shi, R. N. Johnston, S. Nishikawa, P. W. K. Lee, et al. Reovirus as an Oncolytic Agent Against Experimental Human Malignant Gliomas J Natl Cancer Inst, June 20, 2001; 93(12): 903 - 912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Dix, S. J. Edwards, and A. W. Braithwaite Does the Antitumor Adenovirus ONYX-015/dl1520 Selectively Target Cells Defective in the p53 Pathway? J. Virol., June 15, 2001; 75(12): 5443 - 5447. [Full Text] [PDF]
|
|
|
|
|
|
Y. Shen, G. Kitzes, J. A. Nye, A. Fattaey, and T. Hermiston Analyses of Single-Amino-Acid Substitution Mutants of Adenovirus Type 5 E1B-55K Protein J. Virol., May 1, 2001; 75(9): 4297 - 4307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Doronin, M. Kuppuswamy, K. Toth, A. E. Tollefson, P. Krajcsi, V. Krougliak, and W. S. M. Wold Tissue-Specific, Tumor-Selective, Replication-Competent Adenovirus Vector for Cancer Gene Therapy J. Virol., April 1, 2001; 75(7): 3314 - 3324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wodarz Viruses as Antitumor Weapons: Defining Conditions for Tumor Remission Cancer Res., April 1, 2001; 61(8): 3501 - 3507. [Abstract] [Full Text]
|
|
|
|
|
|
A. Sigal and V. Rotter Oncogenic Mutations of the p53 Tumor Suppressor: The Demons of the Guardian of the Genome Cancer Res., December 1, 2000; 60(24): 6788 - 6793. [Abstract] [Full Text]
|
|
|
|
|
|
C. Heise, M. Lemmon, and D. Kirn Efficacy with a Replication-selective Adenovirus Plus Cisplatin-based Chemotherapy: Dependence on Sequencing but not p53 Functional Status or Route of Administration Clin. Cancer Res., December 1, 2000; 6(12): 4908 - 4914. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
