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Science 24 March 2006:
Vol. 311. no. 5768, pp. 1780 - 1784
DOI: 10.1126/science.1121411
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Reports

Synergistic Antitumor Effects of Immune Cell-Viral Biotherapy

Steve H. Thorne,1 Robert S. Negrin,2 Christopher H. Contag1*

Targeted biological therapies hold tremendous potential for treatment of cancer, yet their use has been limited by constraints on delivery and effective tumor targeting. We combined an immune effector cell population [cytokine-induced killer (CIK) cells] with an oncolytic viral therapy to achieve directed delivery to, and regression of, tumors in both immunodeficient and immunocompetent mouse models. Preinfection of CIK cells with modified vaccinia virus resulted in a prolonged eclipse phase with the virus remaining hidden until interaction with the tumor. Whole-body imaging revealed that the cells retained their ability to traffic to and to infiltrate the tumor effectively before releasing the virus. These results illustrate the potential of combining biotherapeutics for synergistic effects that more effectively treat cancer.

1 Departments of Pediatrics, Radiology, Microbiology, and Immunology Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Department of Medicine and Division of Bone Marrow Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA.

* To whom correspondence should be addressed. E-mail: ccontag{at}cmgm.stanford.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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J. Immunol. 180, 6018-6026
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Enhancing Poxvirus Oncolytic Effects through Increased Spread and Immune Evasion.
D. H. Kirn, Y. Wang, W. Liang, C. H. Contag, and S. H. Thorne (2008)
Cancer Res. 68, 2071-2075
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Gene therapy in head and neck cancer: a review.
E Chisholm, U Bapat, C Chisholm, G Alusi, and G Vassaux (2007)
Postgrad. Med. J. 83, 731-737
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Whole-Body Optical Imaging in Animal Models to Assess Cancer Development and Progression.
E. L. Kaijzel, G. van der Pluijm, and C. W.G.M. Lowik (2007)
Clin. Cancer Res. 13, 3490-3497
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Therapeutic Efficacy of Replication-Competent Retrovirus Vector-Mediated Suicide Gene Therapy in a Multifocal Colorectal Cancer Metastasis Model.
K. Hiraoka, T. Kimura, C. R. Logg, C.-K. Tai, K. Haga, G. W. Lawson, and N. Kasahara (2007)
Cancer Res. 67, 5345-5353
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Cytokine-induced killer T cells kill immature dendritic cells by TCR-independent and perforin-dependent mechanisms.
P. S. Joshi, J.-Q. Liu, Y. Wang, X. Chang, J. Richards, E. Assarsson, F.-D. Shi, H.-G. Ljunggren, and X.-F. Bai (2006)
J. Leukoc. Biol. 80, 1345-1353
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Minerva.
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BMJ 332, 982
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Novel "Trojan Horse" Technique Treats Cancer in Mice.
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Journal Watch (General) 2006, 6
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Science. ISSN 0036-8075 (print), 1095-9203 (online)