| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Surgery and
Department of Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA; and
Department of Microbiology and Immunology and
§ Department of Neuroscience, University of Rochester Medical Center, Rochester, New York 14642, USA
1Correspondence: Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA. E-mail: fongy{at}mskcc.org
G207 is a multi-mutated, replication-competent type-1 herpes simplex virus designed to target, infect, and lyse neurological tumors. This study examines the feasibility of using G207 in the treatment of human colorectal cancer and defines the biological determinants of its antitumor efficacy. This virus was tested on five human colorectal cancer cell lines in vitro to determine efficacy of infection and tumor cell kill. These results were correlated to measures of tumor cell proliferation. In vivo testing was performed through direct injections of G207 into xenografts of human colorectal cancer tumors grown in flanks of athymic rats. To evaluate an alternate method of administration, hepatic portal vein infusion of G207 was performed in a syngeneic model of liver metastases in Buffalo rats. Among the five cell lines tested, infection rates ranged between 10% and 90%, which correlated directly with S-phase fraction (8.6%–36.6%) and was proportional to response to G207 therapy in vitro (1%–93%). Direct injection of G207 into nude rat flank tumors suppressed tumor growth significantly vs. control (0.58 ± 0.60 cm3 vs. 9.16 ± 3.70 cm3, P<0. 0001). In vivo tumor suppression correlated with in vitro effect. In the syngeneic liver tumor model, portal infusion resulted in significant reduction in number of liver nodules (13 ± 10 nodules in G207-treated livers vs. 80 ± 30 nodules in control livers, P<0.05). G207 infects and kills human colorectal cancer cells efficiently. In vitro cytotoxicity assay and tumor S-phase fraction can be used to predict response to treatment in vivo. This antineoplastic agent can be delivered effectively by both direct tumor injection and regional vascular infusion. G207 should be investigated further as therapy for colorectal cancer and liver metastases.—Kooby, D. A., Carew, J. F., Halterman, M. W., Mack, J. E., Bertino, J. R., Blumgart, L. H., Federoff, H. J., Fong, Y. Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207).
Key Words: attenuated virus • gene therapy • hepatobiliary tumors • replication • competent
This article has been cited by other articles:
|
|
 |
|
  Y. Woo, K. J. Kelly, M. M. Stanford, C. Galanis, Y. S. Chun, Y. Fong, and G. McFadden Myxoma Virus Is Oncolytic for Human Pancreatic Adenocarcinoma Cells Ann. Surg. Oncol., August 1, 2008; 15(8): 2329 - 2335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kelly, P. Brader, A. Rein, J. P. Shah, R. J. Wong, Y. Fong, and Z. Gil Attenuated multimutated herpes simplex virus-1 effectively treats prostate carcinomas with neural invasion while preserving nerve function FASEB J, June 1, 2008; 22(6): 1839 - 1848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yu, S. Li, Y.-Y. Huang, S.-F. Lin, Y. Fong, and R. J. Wong Sensitivity of Squamous Cell Carcinoma Lymph Node Metastases to Herpes Oncolytic Therapy Clin. Cancer Res., March 15, 2008; 14(6): 1897 - 1904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-F. Lin, S. P. Gao, D. L. Price, S. Li, T.-C. Chou, P. Singh, Y.-Y. Huang, Y. Fong, and R. J. Wong Synergy of a Herpes Oncolytic Virus and Paclitaxel for Anaplastic Thyroid Cancer Clin. Cancer Res., March 1, 2008; 14(5): 1519 - 1528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Gil, A. Rein, P. Brader, S. Li, J. P. Shah, Y. Fong, and R. J. Wong Nerve-Sparing Therapy with Oncolytic Herpes Virus for Cancers with Neural Invasion Clin. Cancer Res., November 1, 2007; 13(21): 6479 - 6485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hiraoka, T. Kimura, C. R. Logg, C.-K. Tai, K. Haga, G. W. Lawson, and N. Kasahara Therapeutic Efficacy of Replication-Competent Retrovirus Vector-Mediated Suicide Gene Therapy in a Multifocal Colorectal Cancer Metastasis Model Cancer Res., June 1, 2007; 67(11): 5345 - 5353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Huang, Z. Yu, S.-F. Lin, S. Li, Y. Fong, and R. J. Wong Nectin-1 Is a Marker of Thyroid Cancer Sensitivity to Herpes Oncolytic Therapy J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1965 - 1970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kuruppu, A.-L. Brownell, A. Zhu, M. Yu, X. Wang, Y. Kulu, B. C. Fuchs, H. Kawasaki, and K. K. Tanabe Positron Emission Tomography of Herpes Simplex Virus 1 Oncolysis Cancer Res., April 1, 2007; 67(7): 3295 - 3300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Adusumilli, B. M. Stiles, M.-K. Chan, T.-C. Chou, R. J. Wong, V. W. Rusch, and Y. Fong Radiation Therapy Potentiates Effective Oncolytic Viral Therapy in the Treatment of Lung Cancer Ann. Thorac. Surg., August 1, 2005; 80(2): 409 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yu, M.-K. Chan, P. O-charoenrat, D. P. Eisenberg, J. P. Shah, B. Singh, Y. Fong, and R. J. Wong Enhanced Nectin-1 Expression and Herpes Oncolytic Sensitivity in Highly Migratory and Invasive Carcinoma Clin. Cancer Res., July 1, 2005; 11(13): 4889 - 4897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Wong, M.-K. Chan, Z. Yu, R. A. Ghossein, I. Ngai, P. S. Adusumilli, B. M. Stiles, J. P. Shah, B. Singh, and Y. Fong Angiogenesis Inhibition by an Oncolytic Herpes Virus Expressing Interleukin 12 Clin. Cancer Res., July 1, 2004; 10(13): 4509 - 4516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kasuya, T. M. Pawlik, J. T. Mullen, J. M. Donahue, H. Nakamura, S. Chandrasekhar, H. Kawasaki, E. Choi, and K. K. Tanabe Selectivity of an Oncolytic Herpes Simplex Virus for Cells Expressing the DF3/MUC1 Antigen Cancer Res., April 1, 2004; 64(7): 2561 - 2567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Wong, M.-K. Chan, Z. Yu, T. H. Kim, A. Bhargava, B. M. Stiles, B. C. Horsburgh, J. P. Shah, R. A. Ghossein, B. Singh, et al. Effective Intravenous Therapy of Murine Pulmonary Metastases with an Oncolytic Herpes Virus Expressing Interleukin 12 Clin. Cancer Res., January 1, 2004; 10(1): 251 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Cohen and N. E. Kemeny An Update on Hepatic Arterial Infusion Chemotherapy for Colorectal Cancer Oncologist, December 1, 2003; 8(6): 553 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Cinatl Jr., J. Cinatl, M. Michaelis, H. Kabickova, R. Kotchetkov, J.-U. Vogel, H. W. Doerr, T. Klingebiel, and P. H. Driever Potent Oncolytic Activity of Multimutated Herpes Simplex Virus G207 in Combination with Vincristine against Human Rhabdomyosarcoma Cancer Res., April 1, 2003; 63(7): 1508 - 1514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Ebright, J. S. Zager, S. Malhotra, K. A. Delman, T. L. Weigel, V. W. Rusch, and Y. Fong Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model J. Thorac. Cardiovasc. Surg., July 1, 2002; 124(1): 123 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Fu and X. Zhang Potent Systemic Antitumor Activity from an Oncolytic Herpes Simplex Virus of Syncytial Phenotype Cancer Res., April 1, 2002; 62(8): 2306 - 2312. [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]
|
|
|
|
 |
|
 H. Petrowsky, G. D. Roberts, D. A. Kooby, B. M. Burt, J. J. Bennett, K. A. Delman, S. F. Stanziale, T. M. Delohery, W. P. Tong, H. J. Federoff, et al. Functional Interaction between Fluorodeoxyuridine-Induced Cellular Alterations and Replication of a Ribonucleotide Reductase-Negative Herpes Simplex Virus J. Virol., August 1, 2001; 75(15): 7050 - 7058. [Abstract] [Full Text]
|
|
|
|
|
|
H. Nakamura, J. T. Mullen, S. Chandrasekhar, T. M. Pawlik, S. S. Yoon, and K. K. Tanabe Multimodality Therapy with a Replication-conditional Herpes Simplex Virus 1 Mutant that Expresses Yeast Cytosine Deaminase for Intratumoral Conversion of 5-Fluorocytosine to 5-Fluorouracil Cancer Res., July 1, 2001; 61(14): 5447 - 5452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Todo, R. L. Martuza, M. J. Dallman, and S. D. Rabkin In Situ Expression of Soluble B7-1 in the Context of Oncolytic Herpes Simplex Virus Induces Potent Antitumor Immunity Cancer Res., January 1, 2001; 61(1): 153 - 161. [Abstract] [Full Text]
|
|
|
|
|
|
G. Coukos, A. Makrigiannakis, E. H. Kang, S. C. Rubin, S. M. Albelda, and K. L. Molnar-Kimber Oncolytic Herpes Simplex Virus-1 Lacking ICP34.5 Induces p53-independent Death and Is Efficacious against Chemotherapy-resistant Ovarian Cancer Clin. Cancer Res., August 1, 2000; 6(8): 3342 - 3353. [Abstract] [Full Text]
|
|
|
|
|
|
T. M. Pawlik, H. Nakamura, S. S. Yoon, J. T. Mullen, S. Chandrasekhar, E. A. Chiocca, and K. K. Tanabe Oncolysis of Diffuse Hepatocellular Carcinoma by Intravascular Administration of a Replication-competent, Genetically Engineered Herpesvirus Cancer Res., June 1, 2000; 60(11): 2790 - 2795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sundaresan, W. D. Hunter, R. L. Martuza, and S. D. Rabkin Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation in Mice J. Virol., April 15, 2000; 74(8): 3832 - 3841. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
