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Intravesical Gene Therapy: In Vivo Gene Transfer Using Recombinant Vaccinia Virus Vectors¹

Division of Neoplastic Diseases, Departments of Medicine [S. S. E., M. J. M., E. C. L.] and Pathology [P. A. M.] and Immunology Program [S. S. L., L. C. E., E. C. L.], Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Intratumoral gene transfer may be a significant tool in active immunotherapy. The ability to insert functional genes into a tumor in vitro and in vivo using recombinant vaccinia vectors was examined in the murine bladder tumor model. Vaccinia recombinants expressing the influenza hemagglutinin or nucleoprotein antigens infected/transfected murine (MB-49 and MBT-2) and human (T24) bladder tumor cell lines in vitro. Systemic vaccinia immunity was induced with as few as 10 plaque-forming units of recombinant vaccinia instilled intravesically, and the encoded protein was expressed in vivo in tumor and urothelium. However, preimmunity to vaccinia did not inhibit intravesical tumor transfection. Thus, recombinant vaccinia virus is effective in introducing foreign antigens locally into tumor in vivo, supporting its use in clinical immunotherapy.

¹ Supported by USPHS Grants CA-42908 and CA-09683. S. S. L. is a Foerderer fellowship recipient.

² To whom requests for reprints should be addressed, at Division of Neoplastic Diseases, Department of Medicine, Thomas Jefferson University, 1015 Walnut St., Suite 1005, Philadelphia, PA 19107.

Received 1/19/94. Accepted 5/16/94.

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