Lipid-protamine-DNA-mediated antigen delivery to antigen-presenting cells results in enhanced anti-tumor immune responses.
Vaccination with antigenic peptides encoding tumor antigens has the potential to be an effective treatment for cancer. To induce tumor-specific cellular immune responses, a peptide antigen must be presented by antigen-presenting cells (APCs) to T-cells in the lymphatic tissues. Effective in vivo delivery of peptide antigens to APCs has been problematic. Here we use a model antigen from the HPV16 E7 protein to formulate LPD/E7 particles that upon iv administration are internalized by CD11c(+) and CD11b(+) cells in the marginal zone of the spleen. Either iv or sc vaccination with LPD/E7 particles induces E7-specific CTL responses stronger than those obtained using previously described liposome/peptide strategies and prevents the establishment of E7-expressing tumors. Furthermore, the administration of LPD/E7 particles to tumor-bearing mice caused complete tumor regression in 100% of the treated animals. Based on these studies, the entrapment of peptide antigens inside LPD particles may be an effective and generally applicable strategy for the enhancement of peptide vaccine potency.
Dileo
John
J
Center for Pharmacogenetics, Department of Pharmaceutical Sciences, Pittsburgh, Pennsylvania 15213, USA.
Banerjee
Rajkumar
R
Whitmore
Mark
M
Nayak
Jayakar V
JV
Falo
Louis D
LD
Huang
Leaf
L
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D005260:Female; D007167:Immunotherapy; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D011479:Protamines; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA
D008081:Liposomes; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011479:Protamines; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16