title: Targeting of antigens to B lymphocytes via CD19 as a means for tumor vaccine development.
abstract: Ab therapy against surface Ags on tumor cells has demonstrated significant efficacy for some cancers. However, it is costly and patients frequently develop acquired resistance over time. In cases of Ab therapy resistance, T cell responses have been shown to be essential in controlling disease progression. Thus, vaccination that generates a sustained Ab response as well as a T cell response may be more effective and economical. In this article, we have developed a vaccination strategy by targeting protein Ags to B cells via a CD19 single-chain variable fragment miniAb. Using the tumor-associated Ag her-2/neu extracellular domain, we showed that the coengagement of CD19 and BCR induced full B cell activation to produce a high titer of Abs and enhanced CD4 Th2 response and CD8 T cell activation and differentiation. These Abs competitively inhibited humanized her-2/neu Ab binding and were capable of activating the complement and inhibiting human breast cancer growth in vitro. Therapeutic efficacy was demonstrated in vivo using murine mammary carcinoma models. Furthermore, four different extracellular domains of her-2/neu could be targeted to B cells to generate Abs against particular domains with different antitumor properties. This approach may offer a new avenue for vaccine development with significantly lower cost, which may be of use not only for cancer therapy but also for infectious agents.
authors: Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors: Yunfeng
authors: Y
authors: Ma
authors: Dong
authors: D
authors: Xiang
authors: Jinwen
authors: J
authors: Sun
authors: Chuanlin
authors: C
authors: Ding
authors: Min
authors: M
authors: Liu
authors: Xiaoling
authors: X
authors: Hu
authors: Guoxin
authors: G
authors: Li
authors: Goetz
authors: G
authors: Kloecker
authors: Huang-Ge
authors: HG
authors: Zhang
authors: Jun
authors: J
authors: Yan
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D018941:Antigens, CD19 / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011485:Protein Binding / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D057127:Single-Chain Antibodies / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D000068878:Trastuzumab; D047368:Tumor Burden / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D018836:Inflammation Mediators; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; D000068878:Trastuzumab
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