Lipid-protamine-DNA-mediated antigen delivery to antigen-presenting cells results in enhanced anti-tumor immune responses

被引:48
作者
Dileo, J
Banerjee, R
Whitmore, M
Nayak, JV
Falo, LD
Huang, L
机构
[1] Univ Pittsburgh, Ctr Pharmacogenet, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Biochem & Mol Genet, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15213 USA
关键词
liposome; LPD; peptide vaccine; E7; HPV; cervical cancer;
D O I
10.1016/S1525-0016(03)00064-9
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:640 / 648
页数:9
相关论文
共 41 条
[1]   DNA vaccination: Transfection and activation of dendritic cells as key events for immunity [J].
Akbari, O ;
Panjwani, N ;
Garcia, S ;
Tascon, R ;
Lowrie, D ;
Stockinger, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (01) :169-177
[2]   A novel liposomal influenza vaccine (INFLUSOME-VAC) containing hemagglutinin-neuraminidase and IL-2 or GM-CSF induces protective anti-neuraminidase antibodies cross-reacting with a wide spectrum of influenza A viral strains [J].
Babai, I ;
Barenholz, Y ;
Zakay-Rones, Z ;
Greenbaum, E ;
Samira, S ;
Hayon, I ;
Rochman, M ;
Kedar, E .
VACCINE, 2001, 20 (3-4) :505-515
[3]   Increased dendritic cell number and function following continuous in vivo infusion of granulocyte macrophage-colony-stimulating factor and interleukin-4 [J].
Basak, SK ;
Harui, A ;
Stolina, M ;
Sharma, S ;
Mitani, K ;
Dubinett, SM ;
Roth, MD .
BLOOD, 2002, 99 (08) :2869-2879
[4]   Dynamical behavior of viscoelastic cylindrical shells under axial pressures [J].
Cheng, CJ ;
Zhang, NH .
APPLIED MATHEMATICS AND MECHANICS-ENGLISH EDITION, 2001, 22 (01) :1-9
[5]   Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen [J].
Cheng, WF ;
Hung, CF ;
Chai, CY ;
Hsu, KF ;
He, LM ;
Ling, M ;
Wu, TC .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 108 (05) :669-678
[6]   DNA-based immunization by in vivo transfection of dendritic cells [J].
Condon, C ;
Watkins, SC ;
Celluzzi, CM ;
Thompson, K ;
Falo, LD .
NATURE MEDICINE, 1996, 2 (10) :1122-1128
[7]   The dendritic cell and human cancer vaccines [J].
Dallal, RM ;
Lotze, MT .
CURRENT OPINION IN IMMUNOLOGY, 2000, 12 (05) :583-588
[8]   VACCINATION WITH CYTOTOXIC T-LYMPHOCYTE EPITOPE-CONTAINING PEPTIDE PROTECTS AGAINST A TUMOR-INDUCED BY HUMAN PAPILLOMAVIRUS TYPE-16-TRANSFORMED CELLS [J].
FELTKAMP, MCW ;
SMITS, HL ;
VIERBOOM, MPM ;
MINNAAR, RP ;
DEJONGH, BM ;
DRIJFHOUT, JW ;
TERSCHEGGET, J ;
MELIEF, CJM ;
KAST, WM .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (09) :2242-2249
[9]   Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer [J].
Güre, AO ;
Stockert, E ;
Scanlan, MJ ;
Keresztes, RS ;
Jäger, D ;
Altorki, NK ;
Old, LJ ;
Chen, YT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (08) :4198-4203
[10]   Immunity against cancer: lessons learned from melanoma [J].
Houghton, AN ;
Gold, JS ;
Blachere, NE .
CURRENT OPINION IN IMMUNOLOGY, 2001, 13 (02) :134-140