Targeted antigen delivery to antigen-presenting cells including dendritic cells by engineered Fas-mediated apoptosis

Michael A. Chattergoon, J. Joseph Kim, Joo Sung Yang, Tara M. Robinson, Daniel J. Lee, Tzvete Dentchev, Darren M. Wilson, Velpandi Ayyavoo, David B. Weiner

Research output: Contribution to journalArticle

Abstract

Immunity to tumors as well as to viral and bacterial pathogens is often mediated by cytotoxic T lymphocytes (CTLs). Thus, the ability to induce a strong cell-mediated immune response is an important requirement of novel immunotherapies. Antigen-presenting cells (APCs), including dendritic cells (DCs), are specialized in initiating T-cell immunity. Harnessing this innate ability of these cells to acquire and present antigens, we sought to improve antigen presentation by targeting antigens directly to DCs in vivo through apoptosis. We engineered Fas-mediated apoptotic death of antigen-bearing cells in vivo by co-expressing the immunogen and Fas in the same cell. We then observed that the death of antigen-bearing cells results in increased antigen acquisition by APCs including DCs. This in vivo strategy led to enhanced antigen-specific CTLs, and the elaboration of T helper-1 (Th1) type cytokines and chemokines. This adjuvant approach has important implications for viral and nonviral delivery strategies for vaccines or gene therapies.

Original languageEnglish (US)
Pages (from-to)974-979
Number of pages6
JournalNature biotechnology
Volume18
Issue number9
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Cytotoxic T-lymphocytes
  • Dendritic cells
  • Fas
  • Vaccines

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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  • Cite this

    Chattergoon, M. A., Kim, J. J., Yang, J. S., Robinson, T. M., Lee, D. J., Dentchev, T., Wilson, D. M., Ayyavoo, V., & Weiner, D. B. (2000). Targeted antigen delivery to antigen-presenting cells including dendritic cells by engineered Fas-mediated apoptosis. Nature biotechnology, 18(9), 974-979. https://doi.org/10.1038/79470