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

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.

• Authors: Takashi Inozume, Hiroshi Mitsui, Takashi Okamoto, Yuriko Matsuzaki, Yutaka Kawakami, Naotaka Shibagaki, Shinji Shimada
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 127 Issue 12 Pg. 2818-22 (Dec 2007) ISSN: 1523-1747 [Electronic] United States
• PMID: 17625599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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