Format

Send to

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2009 Jul 15;15(14):4612-21. doi: 10.1158/1078-0432.CCR-08-3321. Epub 2009 Jul 7.

Targeted delivery of tumor antigens to activated dendritic cells via CD11c molecules induces potent antitumor immunity in mice.

Author information

  • 1International Joint Cancer Institute and Shanghai Key Laboratory of Cell Engineering and Antibody, The Second Military Medical Universit, Shanghai, People's Republic of China.

Abstract

PURPOSE:

CD11c is an antigen receptor predominantly expressed on dendritic cells (DC), to which antigen targeting has been shown to induce robust antigen-specific immune responses. To facilitate targeted delivery of tumor antigens to DCs, we generated fusion proteins consisting of the extracellular domain of human HER or its rat homologue neu, fused to the single-chain fragment variable specific for CD11c (scFv(CD11c)-HER2/neu).

EXPERIMENTAL DESIGN:

Induction of cellular and humoral immune responses and antitumoral activity of the fusion proteins admixed with DC-activating CpG oligonucleotides (scFv(CD11c)-HER2/neu(CpG)) were tested in transplantable HER2/neu-expressing murine tumor models and in transgenic BALB-neuT mice developing spontaneous neu-driven mammary carcinomas.

RESULTS:

Vaccination of BALB/c mice with scFv(CD11c)-HER2(CpG) protected mice from subsequent challenge with HER2-positive, but not HER2-negative, murine breast tumor cells, accompanied by induction of strong HER2-specific T-cell and antibody responses. In a therapeutic setting, injection of scFv(CD11c)-HER2(CpG) caused rejection of established HER2-positive tumors. Importantly, antitumoral activity of such a fusion protein vaccine could be reproduced in immunotolerant BALB-neuT mice, where scFv(CD11c)-neu(CpG) vaccination significantly protected against a subsequent challenge with neu-expressing murine breast tumor cells and markedly delayed the onset of spontaneous mammary carcinomas.

CONCLUSIONS:

CD11c-targeted protein vaccines for in vivo delivery of tumor antigens to DCs induce potent immune responses and antitumoral activities and provide a rationale for further development of this approach for cancer immunotherapy.

PMID:
19584156
DOI:
10.1158/1078-0432.CCR-08-3321
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center