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Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine

Gene Therapy volume 9, pages 1302–1311 (2002)Cite this article

Abstract

Cancer vaccines composed of tumor cells engineered to secrete granulocyte–macrophage colony-stimulating factor (GM-CSF) are currently being clinically evaluated. To enhance the immunogenicity of GM-CSF-secreting tumor cell vaccines, a novel approach expressing GM-CSF as a membrane-bound form (mbGM-CSF) on the tumor cell surface was investigated. The intent was to enhance antigen presentation by increasing interactions between the tumor cell lines in the vaccine and GM-CSF receptor positive antigen presenting cells (APC), notably the patient's Langerhans cells residing within the intradermal injection site. B16.F10 cells engineered to express either membrane-bound or secreted GM-CSF were compared in the B16.F10 mouse melanoma model. We observed that mbGM-CSF on the tumor cell surface retarded growth and induced protective immunity to subsequent wild-type tumor challenge more effectively than tumor cells secreting GM-CSF. Vaccination with irradiated mbGM-CSF B16.F10 also provided strong protection from wild-type tumor challenge, improved therapeutic effects against established tumors, and retarded lung metastases. These results demonstrate that mbGM-CSF B16.F10 cells can induce strong systemic immunity that protects against and therapeutically treats B16.F10 melanoma more effectively than analogous vaccines containing only secreted GM-CSF. These data warrant further development and clinical testing of mbGM-CSF tumor cell vaccines.

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Acknowledgements

The authors wish to acknowledge Katherine Lundeen for construction of mbGM-CSF and secGM-CSF B16.F10 cell lines and Wiesia Giermakowska for additional FACS analysis support. We also thank Dr Georgia Theofan for critical review and helpful discussion in preparing this manuscript, and Joanne Owen and Michele Harden for secretarial support.

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  1. Division of Cancer, The Immune Response Corporation, Carlsbad, CA, USA

    S Yei, R M Bartholomew, P Pezzoli, A Gutierrez, E Gouveia, D Bassett, W Soo Hoo & D J Carlo

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  1. S Yei
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  2. R M Bartholomew
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Yei, S., Bartholomew, R., Pezzoli, P. et al. Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine. Gene Ther 9, 1302–1311 (2002). https://doi.org/10.1038/sj.gt.3301803

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