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Tumor cells engineered to codisplay on their surface 4-1BBL and LIGHT costimulatory proteins as a novel vaccine approach for cancer immunotherapy

Cancer Gene Therapy volume 17, pages 730–741 (2010)Cite this article

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Abstract

Primary tumor cells genetically modified to express a collection of immunological ligands on their surface may have the utility as therapeutic autologous cancer vaccines. However, genetic modification of primary tumor cells is not only cost, labor and time intensive, but also has safety repercussions. As an alternative, we developed the ProtEx technology that involves generation of immunological ligands with core streptavidin (SA) and their display on biotinylated cells in a rapid and efficient manner. We herein demonstrate that TC-1 tumor cells can be rapidly and efficiently engineered to codisplay on their surface two costimulatory proteins, SA-4-1BBL and SA-LIGHT, simultaneously. Vaccination with irradiated TC-1 cells codisplaying both chimeric proteins showed 100% efficacy in a prophylactic and >55% efficacy in a therapeutic tumor setting. In contrast, vaccination with TC-1 cells engineered with either protein alone showed significantly reduced efficacy in the prophylactic setting. Vaccine efficacy was associated with the generation of primary and memory T-cell and antibody responses against the tumor without detectable signs of autoimmunity. Engineering tumor cells in a rapid and effective manner to simultaneously display on their surface a collection of immunostimulatory proteins with additive/synergistic functions presents a novel alternative approach to gene therapy with considerable potential for cancer immunotherapy.

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Acknowledgements

We thank O Grimany for his technical assistance in proteins production and purification. This work was funded, in part, by grants from the NIH (R43 AI071618, R41 CA121665, R44 AI071618 and R43AI074176), the Kentucky Lung Cancer Research Program, WM Keck Foundation and the Commonwealth of Kentucky Research Challenge Trust Fund.

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  1. K G Elpek

    Present address: 2Current address: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.,

Authors and Affiliations

  1. Department of Microbiology and Immunology and James Graham Brown Cancer Center, Institute for Cellular Therapeutics, University of Louisville, Louisville, KY, USA

    R K Sharma, E S Yolcu, K G Elpek & H Shirwan

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  1. R K Sharma
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Correspondence to H Shirwan.

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Competing interests

The SA-4-1BBL described in this paper is licensed from UofL by ApoImmune, Inc, Louisville, KY, for which Haval Shirwan serves as CSO, and Haval Shirwan and Esma S Yolcu have significant equity interest in the Company. The remaining authors declare no conflict of interest.

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Sharma, R., Yolcu, E., Elpek, K. et al. Tumor cells engineered to codisplay on their surface 4-1BBL and LIGHT costimulatory proteins as a novel vaccine approach for cancer immunotherapy. Cancer Gene Ther 17, 730–741 (2010). https://doi.org/10.1038/cgt.2010.29

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