Dendritic cells transduced with autoantigen FCRLA induce cytotoxic lymphocytes and vaccinate against murine B-cell lymphoma.
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.
Inozume
Takashi
T
Faculty of Medicine, Department of Dermatology, University of Yamanashi, Yamanashi, Japan.
Mitsui
Hiroshi
H
Okamoto
Takashi
T
Matsuzaki
Yuriko
Y
Kawakami
Yutaka
Y
Shibagaki
Naotaka
N
Shimada
Shinji
S
D000818:Animals; D001324:Autoantigens / Q000737:chemistry*; D019496:Cancer Vaccines / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation; D007167:Immunotherapy / Q000379:methods; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D011961:Receptors, Fc / Q000096:biosynthesis*; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000378:metabolism
D001324:Autoantigens; D019496:Cancer Vaccines; C452186:FCRLA protein, human; C524782:Fcrla protein, mouse; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins