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Liposome-polycation-DNA (LPD) particle as a carrier and adjuvant for protein-based vaccines: Therapeutic effect against cervical cancer

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Abstract

With the successful identification of many tumor-specific antigens, tumor-associated antigens, and the potential of using unfractioned tumor cell derivatives as tumor antigens, a system and/or adjuvant that can deliver these antigens and help them to induce strong and effective anti-tumor immune responses is greatly needed. Previously, we reported that a MHC class I-restricted peptide epitope derived from human papillomavirus (HPV) 16 E7 protein, when incorporated into a clinically proven safe LPD (liposome-polycation-DNA) particle, was able to effectively eradicate tumors established in mice. Cervical cancer is the second most common cancer among women worldwide. HPV infection is clearly linked to this cancer. Vaccines based on the early (E) gene products of HPV could be effective in controlling it. However, besides the fact that epitope vaccines have many limitations particularly, concerning the diverse HLAs in humans, the use of the epitope as an antigen prevented us from fully characterizing the immune responses induced by the LPD as a vaccine carrier and/or adjuvant in previous studies. In the present study, by using the HPV 16 E7 protein as an antigen, we first showed that LPD, as a vaccine carrier and adjuvant induced strong and robust immune responses, both cellular and antibody. We then showed that immunization with LPD particles incorporated with either the wild type HPV 16 E7 protein or a potentially safer mutant induced strong immune responses that caused complete regressions of a model cervical cancer tumor established in murines. LPD could be a potent vaccine carrier and/or adjuvant for many antigens.

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Acknowledgment

This work was supported in part by NIH grants CA74918 and AI48851 to LH. The authors would like to thank Dr. Jeong-Im Sin from the Catholic University of Korea (Seoul, Korea) for the pET-E7 plasmid. ZRC would like to thank Jiang Li and Bin Sun for their help in plasmid molecular manipulation.

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  1. Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, 633 Salk Hall, Pittsburgh, PA, 15213, USA

    Zhengrong Cui & Leaf Huang

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, 97331, USA

    Zhengrong Cui

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Cui, Z., Huang, L. Liposome-polycation-DNA (LPD) particle as a carrier and adjuvant for protein-based vaccines: Therapeutic effect against cervical cancer. Cancer Immunol Immunother 54, 1180–1190 (2005). https://doi.org/10.1007/s00262-005-0685-2

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