Systemic long-term delivery of antibodies in immunocompetent animals using cellulose sulphate capsules containing antibody-producing cells

被引:50
作者
Pelegrin, M
Marin, M
Noel, D
Del Rio, M
Saller, R
Stange, J
Mitzner, S
Gunzburg, WH
Piechaczyk, M
机构
[1] Inst Genet Mol Montpellier, UMR 5535,IFR 24, F-34293 Montpellier 05, France
[2] UFR Sci Pharmaceut & Biol, UMR 9921, Montpellier, France
[3] Bavarian Nord, Munchen, Germany
[4] Innere Med Klin, Rostock, Germany
[5] Univ Vet Sci, Vienna, Austria
关键词
antibody delivery; anti-idiotypic response; capsules; hybridoma; cellulose sulphate matrix;
D O I
10.1038/sj.gt.3300632
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Implantation of capsules containing antibody-producing cells into patients would potentially permit systemic long-term delivery of antibodies and might, thus, be useful in the development of surveillance treatments for cancers and severe viral diseases. We show that cellulose sulphate (CS) capsules containing hybridoma cells, when implanted subcutaneously or in the intraperitoneal cavity, can be used for delivering monoclonal antibodies into the bloodstream of immunocompetent mice for at least several months. In contrast to capsules implanted into the intraperitoneal cavity, which remain mobile and nonvascularized, capsules implanted under the skin form neo-organs which become vascularized within days. This may explain the higher blood concentration of the antibody we have observed in the latter case. Importantly, neither an isolating fibrosis nor an obvious inflammatory response was detected at the capsule implantation sites during observation periods as long as 10 months. finally, no anti-idiotypic immune response against the ectopically delivered antibody was shown to occur. this rules out any potent adjuvant effect of the cellulose sulphate matrix that might have stimulated a neutralizing humoral response. Taken together, out data indicate that encapsulation of antibody-producing cells into CS might be used in antibody-based gene/cell therapy approaches.
引用
收藏
页码:828 / 834
页数:7
相关论文
共 26 条
  • [1] TRANSPLANTATION OF NEURAL TISSUE IN POLYMER CAPSULES
    AEBISCHER, P
    WINN, SR
    GALLETTI, PM
    [J]. BRAIN RESEARCH, 1988, 448 (02) : 364 - 368
  • [2] Chang PL, 1995, SOMATIC GENE THERAPY, P203
  • [3] TRANSFER OF GENES TO HUMANS - EARLY LESSONS AND OBSTACLES TO SUCCESS
    CRYSTAL, RG
    [J]. SCIENCE, 1995, 270 (5235) : 404 - 410
  • [4] DELRIO M, 1995, IMMUNOL INVEST, V24, P655
  • [5] DURRANT LG, 1989, CANCER IMMUNOL IMMUN, V28, P37
  • [6] Gunzburg WH, 1996, J MOL MED, V74, P171
  • [7] Harlow E., 1988, ANTIBODIES LAB MANUA, P298
  • [8] Strategies for targeted gene therapy
    Harris, JD
    Lemoine, NR
    [J]. TRENDS IN GENETICS, 1996, 12 (10) : 400 - 405
  • [9] Isaacs J D, 1990, Semin Immunol, V2, P449
  • [10] Increased clearance of IgG in mice that lack beta(2)-microglobulin: Possible protective role of FcRn
    Israel, EJ
    Wilsker, DF
    Hayes, KC
    Schoenfeld, D
    Simister, NE
    [J]. IMMUNOLOGY, 1996, 89 (04) : 573 - 578