Liposome-polycation-DNA (LPD) particle as a carrier and adjuvant for protein-based vaccines: therapeutic effect against cervical cancer.
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.
Cui
Zhengrong
Z
Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, 633 Salk Hall, Pittsburgh, PA 15213, USA. zhengrong.cui@oregonstate.edu
Huang
Leaf
L
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D004337:Drug Carriers; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D008081:Liposomes / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D050725:Papillomavirus E7 Proteins; D010957:Plasmids / Q000627:therapeutic use*; D017354:Point Mutation; D011479:Protamines / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D004337:Drug Carriers; D008081:Liposomes; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011479:Protamines; C059731:oncogene protein E7, Human papillomavirus type 16