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In Vivo Molecular Therapy with p53 Adenovirus for Microscopic Residual Head and Neck Squamous Carcinoma¹

Department of Head and Neck Surgery [G. L. C., H. G., D. L. T., T-J. L.], Pathology [A. K. E.], and Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery [W. W. Z., J. A. R.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Developing gene therapy strategies may allow contemporary medicine to reassess its management of solid malignancies. We have demonstrated previously that the wild-type p53 adenovirus (Ad5CMV-p53) suppressed the growth of established tumors of the head and neck. In this paper we develop a microscopic residual model which mimics the postsurgical environment of head and neck cancer patients with advanced disease. Using this squamous cell carcinoma of the head and neck model, we prevented the establishment of tumors in nude mice in which tumor cells had been s.c. implanted by transiently introducing exogenous wild-type p53 via an adenoviral vector 2 days following tumor cell implantation. These effects were vector dose dependent but independent on the endogenous wild-type or mutated p53 status of the cells. Importantly, karyotypically normal and nontumorigenic fibroblast cell lines are inert to the p53 adenovirus treatment. These results pave the ground work for further development of molecular therapy for head and neck cancer and other solid malignancies.

¹ This work was supported in part by American Cancer Society Career Development Award 93-9 (G. L. C.); M. D. Anderson Cancer Center Core Grant NIH-National Cancer Institute CA-16672; National Cancer Institute Grant R01 CA-45187 (J.A.R.); Training Grant CA09611 (J. A. R.); gifts to the Division of Surgery from Tenneco and Exxon for the Core Lab Facility; and a generous gift from the Mathers Foundation.

² To whom requests for reprints should be addressed, at M. D. Anderson Cancer Center, Department of Head and Neck Surgery, Box 69, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 10/11/94. Accepted 10/31/94.

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