Targeted delivery of diphtheria toxin via immunoliposomes: efficient antitumor activity in the presence of inactivating anti‐diphtheria toxin antibodies

FEBS Letters

Hendriks, Jos J.G.W¹  Crommelin, Daan J.A²  Vingerhoeds, Monique H²  Steerenberg, Peter A¹  Storm, Gert² 

[1]Laboratory for Pathology, National Institute of Public Health and Environmental Protection, P.O. Box 1, 3720 BA Bilthoven, The Netherlands

[2]Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands

关键词: Diphtheria toxin;    Immunoliposome;    Targeted drug delivery;    Monoclonal antibody;    Ovarian cancer;    AT antibodies;    anti-diphtheria toxin antibodies;    AU;    antibody unit;    CHOL;    cholesterol;    DMEM;    Dulbecco's modified Eagle's medium;    DT;    diphtheria toxin;    DTA;    diphtheria toxin fragment A;    DTT;    dithiothreitol;    EPC;    egg phosphatidylcholine;    EPG;    egg phosphatidylglycerol;    FCS;    fetal calf serum;    Lf;    limit of flocculation (quantity of DT that flocculates most rapidly when mixed with 1 unit of antitoxin);    MPB-PE;    N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine;    PE;    phosphatidylethanolamine;    SMPB;    succinimidyl 4-(p-maleimidophenyl)butyrate;    SRB;    sulforhodamine-B;    TL;    total lipid (phospholipid+cholesterol);   

DOI  :  10.1016/0014-5793(96)01055-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Diphtheria toxin (DT) has attracted considerable attention for anti-cancer therapy. However, its extensive use is prohibited by (i) its non-specific action which can result in substantial toxicity, (ii) most patients have low serum levels of anti-DT antibodies (AT antibodies) which can inactivate DT and (iii) its immunogenicity will boost the circulating AT antibody level, thereby further compromising the antitumor activity. To overcome these limitations, we have developed a new approach for targeted delivery of DT utilizing immunoliposomes. In this approach, protection against the non-specific action of DT is combined with efficient antitumor activity even in the presence of inactivating AT antibodies.

【 授权许可】

Unknown