Human scFv SIgA expressed on Lactococcus lactis as a vector for the treatment of mucosal disease

被引:9
作者
Yuvaraj, Saravanan [1 ]
Lahham, Saed [1 ]
Marreddy, Ravi K. R. [2 ]
Dijkstra, Gerard [3 ]
Wolken, Wout A. M.
Lolkema, Juke S.
Helfrich, Wijnand [4 ]
Johansen, Finn-Erik [5 ]
Peppelenbosch, Maikel P. [1 ]
Bos, Nicolaas A. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Immunol Sect, Dept Cell Biol, NL-9713 AV Groningen, Netherlands
[2] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Dept Biochem, NL-9713 AV Groningen, Netherlands
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, NL-9713 AV Groningen, Netherlands
[4] Univ Groningen, Univ Med Ctr Groningen, Sect Med Biol, Lab Tumor Immunol,Dept Pathol & Lab Med, NL-9713 AV Groningen, Netherlands
[5] Univ Oslo, Rikshosp Radiumhosp Med Ctr, Inst Pathol, Lab Immunohistochem & Immunopathol, Oslo, Norway
关键词
Lactococcus lactis; local delivery system; pIgR; recombinant; ScFv SIgA;
D O I
10.1002/mnfr.200700132
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
The gastrointestinal tract is a complex niche and the main port of entry of many pathogens that trigger a wide range of diseases like inflammatory bowel disease (IBD) and colon cancer. Antibodies are effective for treating such diseases, but a System capable of local delivery at the site of the pathology, thus avoiding systemic side effects, is not yet available. Here we report a novel recombinant scFvSIgA1 protein produced by Lactococcus lactis, anchored to the bacterial membrane, which retains its full immuno-recognizing potential. This scFv fragment employed was specific for a colon cancer epilope, epithelial glycoprotein protein-2 (EGP-2). Accordingly L. lactis expressing this chimeric protein was capable of binding cells expressing this epitope. Expression of specific antibodies on bacteria may allow local delivery of anticancer agents produced by Such bacteria ill Conjunction with the antibody and provides a new avenue in the quest for targeted drug delivery.
引用
收藏
页码:913 / 920
页数:8
相关论文
共 31 条
[1]   A comparison of the binding of secretory component to immunoglobulin A (IgA) in human colostral S-IgA1 and S-IgA2 [J].
Almogren, Adel ;
Senior, Bernard W. ;
Kerr, Michael A. .
IMMUNOLOGY, 2007, 120 (02) :273-280
[2]  
Alvarez RD, 2000, CLIN CANCER RES, V6, P3081
[3]   The biology of the 17-1A antigen (Ep-CAM) [J].
Balzar, M ;
Winter, MJ ;
de Boer, CJ ;
Litvinov, SV .
JOURNAL OF MOLECULAR MEDICINE-JMM, 1999, 77 (10) :699-712
[4]   The conserved C-terninus of the citrate (CitP) and malate (MleP) transporters of lactic acid bacteria is involved in substrate recognition [J].
Bandell, M ;
Lolkema, JS .
BIOCHEMISTRY, 2000, 39 (42) :13059-13067
[5]   Immunology of Crohn's disease [J].
Braat, Henri ;
Peppelenbosch, Maikel P. ;
Hommes, Daan W. .
INFLAMMATORY BOWEL DISEASE: GENETICS, BARRIER FUNCTION, IMMUNOLOGIC MECHANISMS, AND MICROBIAL PATHWAYS, 2006, 1072 :135-154
[6]   A phase I trial with Transgenic bacteria expressing interleukin-10 in Crohn's disease [J].
Braat, Henri ;
Rottiers, Pieter ;
Hommes, Daniel W. ;
Huyghebaert, Nathalie ;
Remaut, Erik ;
Remon, Jean-Paul ;
Van Deventer, Sander J. H. ;
Neirynck, Sabine ;
Peppelenbosch, Maikel P. ;
Steidler, Lothar .
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2006, 4 (06) :754-759
[7]   The B-cell system of human mucosae and exocrine glands [J].
Brandtzaeg, P ;
Farstad, IN ;
Johansen, FE ;
Morton, HC ;
Norderhaug, IN ;
Yamanaka, T .
IMMUNOLOGICAL REVIEWS, 1999, 171 :45-87
[8]   CM-restricted activation of Fas-mediated apoptosis: a novel therapeutic approach for acute T-cell leukemia [J].
Bremer, E ;
ten Cate, B ;
Samplonius, DF ;
de Leij, LFMH ;
Helfrich, W .
BLOOD, 2006, 107 (07) :2863-2870
[9]   Exceptionally potent anti-tumor bystander activity of an scFv:sTRAIL fusion protein with specificity for EGP2 toward target antigen-negative tumor cells [J].
Bremer, E ;
Samplonius, D ;
Kroesen, BJ ;
van Genne, L ;
de Leij, L ;
Helfrich, W .
NEOPLASIA, 2004, 6 (05) :636-645
[10]   Controlled gene expression systems for Lactococcus lactis with the food-grade inducer nisin [J].
deRuyter, PGGA ;
Kuipers, OP ;
deVos, WM .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 1996, 62 (10) :3662-3667