Dendritic cells transduced with autoantigen FCRLA induce cytotoxic lymphocytes and vaccinate against murine B-cell lymphoma

J Invest Dermatol. 2007 Dec;127(12):2818-22. doi: 10.1038/sj.jid.5700909. Epub 2007 Jul 12.

Abstract

We previously reported early evidence of the human Fc receptor-like A (hFCRLA), an antigen (Ag) that was specifically expressed in melanocytes, melanoma cells, and some B-cell states, and was recognized by IgG antibodies from melanoma patients. Recently, it has been demonstrated that hFCRLA is expressed in most human B-cell lymphoma tissues. In this report, we investigated the potential of FCRLA as a tumor-associated Ag of B-cell lymphoma for immunotherapy. We confirmed that murine FCRLA (mFCRLA) was expressed and distributed in murine tissues similar to hFCRLA. Recombinant mFCRLA fusion protein was constructed with a polyarginine (R9)-protein-transduction domain (PTD) (rR9-HA-mFCRL), and was transduced into bone marrow-derived dendritic cells (DC) ex vivo. Mice immunized with rR9-HA-mFCRL-treated DC primed cytotoxic T-lymphocyte (CTL) that killed the B-cell lymphoma cell line (A20), which express mFCRLA abundantly. In a tumor challenging study, A20 tumor growth inoculated in skin was significantly suppressed in mice vaccinated with rR9-HA-mFCRL-treated DC, compared with control mice. These results indicated that FCRLA is a potential target Ag in immunotherapy for B-cell lymphoma. In addition, our experimental system using R9-PTD-containing full-length proteins might be a useful method to analyze the immunogenicity of novel candidates of tumor-associated Ags in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / chemistry*
  • Cancer Vaccines / chemistry
  • Dendritic Cells / cytology*
  • Female
  • Gene Expression Regulation*
  • Immunotherapy / methods
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Fc / biosynthesis*
  • Receptors, Immunologic / biosynthesis*
  • Receptors, Immunologic / genetics*
  • Recombinant Fusion Proteins / chemistry
  • T-Lymphocytes, Cytotoxic / cytology*
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Autoantigens
  • Cancer Vaccines
  • FCRLA protein, human
  • Fcrla protein, mouse
  • Receptors, Fc
  • Receptors, Immunologic
  • Recombinant Fusion Proteins