Recombinant influenza viruses expressing tumor-associated antigens as antitumor agents

Abstract

The present invention relates to the engineering of recombinant influenza viruses that express tumor-associated antigens. Expression of tumor-associated antigens by these viruses can be achieved by engineering specific epitopes into influenza virus proteins, or by engineering viral genes that encode a viral protein and the specific antigen as independent polypeptides. Tumor-bearing patients can be immunized with the recombinant influenza viruses alone, or in combination with another treatment, to induce an immune response that leads to tumor reduction. The recombinant viruses can also be used to vaccinate high risk tumor-free patients to prevent tumor formation in vivo.

Description

[0001] This application claims priority to U.S. provisional application Ser. No. 60 / 045,176, filed Apr. 30, 1997, incorporated by reference herein, in its entirety. The work reflected in this application was supported, in part, by a grant from the National Institutes of Health, and the Government may have certain rights in the invention.1. INTRODUCTION[0002] The present invention relates to the engineering of recombinant influenza viruses that express tumor-associated antigens. Expression of tumor-associated antigens by these viruses can be achieved by engineering specific epitopes into influenza virus proteins, or by engineering viral genes that encode a viral protein and the specific antigen as independent polypeptides. Tumor-bearing patients can be immunized with the recombinant influenza viruses alone, or in combination with another treatment, to induce an immune response that leads to tumor reduction. The recombinant viruses can also be used to vaccinate high risk tumor-free pa...

AI Technical Summary

Benefits of technology

[0008] Expression of TAAs by these viruses can be achieved by engineering specific TAA epitopes into the influenza virus proteins, or by engineering viral genes that encode a viral protein and the specific antigen as independent polypeptides. The methods of the present invention permit the generation of stable recombinant viruses expressing foreign epitopes and / or polypeptides.

[0010] The invention is based, in part, on the surprising discovery that the recombinant influenza viruses of the invention induce a potent and specific cell-mediated immune response directed against the tumor cells resulting in tumor reduction. The invention is also based, in part, on the recognition that non-transmissible attenuated strains of influenza virus could be used to engineer vaccines for use in humans. Moreover, since influenza viruses change their antigenic determinants very quickly, different viral strains can be selected and engineered for use to avoid the presence of pre-existing immunity against the virus in patients. Strain variability permits the construction of a vast repertoire of vaccine formulations, and obviates the problems of host resistance.

Problems solved by technology

A number of immunotherapeutic approaches proposed for the treatment of tumors have had limited success.

However, successful treatment has been hampered, in part, by the relative inaccessibility of the tumor cells to the circulating, exogenously administered antibodies.

However, the foregoing systems have limitations which restrict their use in humans.

In addition, the pathogenicity associated with some virus vectors, e.g., adenoviruses, also severely limit their use in vaccine formulations for human patients.

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