التفاصيل البيبلوغرافية
العنوان: |
Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor. |
المؤلفون: |
Baral, Toya Nath, Magez, Stefan, Stijlemans, Benoît, Conrath, Katja, Vanhollebeke, Benoît, Pays, Etienne, Muyldermans, Serge, De Baetselier, Patrick |
المصدر: |
Nature medicine, 12 (5 |
سنة النشر: |
2006 |
المجموعة: |
DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
مصطلحات موضوعية: |
Sciences bio-médicales et agricoles, Animals, Antibodies, Protozoan -- immunology, Apolipoproteins -- genetics, Apolipoproteins -- immunology, Humans, Immunoglobulin Heavy Chains -- immunology, Immunotoxins -- therapeutic use, Lipoproteins, HDL -- genetics, HDL -- immunology, Mice, Inbred C57BL, Molecular Sequence Data, Trypanocidal Agents -- immunology, Trypanocidal Agents -- therapeutic use, Trypanosoma brucei rhodesiense -- immunology, Trypanosoma brucei rhodesiense -- metabolism, Trypanosomiasis, African -- drug therapy, African -- immunology, Variant Surface Glycoproteins, Trypanosoma -- genetics, Trypanosoma -- immunology |
الوصف: |
High systemic drug toxicity and increasing prevalence of drug resistance hampers efficient treatment of human African trypanosomiasis (HAT). Hence, development of new highly specific trypanocidal drugs is necessary. Normal human serum (NHS) contains apolipoprotein L-I (apoL-I), which lyses African trypanosomes except resistant forms such as Trypanosoma brucei rhodesiense. T. b. rhodesiense expresses the apoL-I-neutralizing serum resistance-associated (SRA) protein, endowing this parasite with the ability to infect humans and cause HAT. A truncated apoL-I (Tr-apoL-I) has been engineered by deleting its SRA-interacting domain, which makes it lytic for T. b. rhodesiense. Here, we conjugated Tr-apoL-I with a single-domain antibody (nanobody) that efficiently targets conserved cryptic epitopes of the variant surface glycoprotein (VSG) of trypanosomes to generate a new manmade type of immunotoxin with potential for trypanosomiasis therapy. Treatment with this engineered conjugate resulted in clear curative and alleviating effects on acute and chronic infections of mice with both NHS-resistant and NHS-sensitive trypanosomes. ; Journal Article ; Research Support, Non-U.S. Gov't ; info:eu-repo/semantics/published |
نوع الوثيقة: |
article in journal/newspaper |
وصف الملف: |
No full-text files |
اللغة: |
English |
Relation: |
uri/info:doi/10.1038/nm1395; uri/info:pii/nm1395; uri/info:pmid/16604085; uri/info:scp/33646545070; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/51563 |
الاتاحة: |
http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/51563 |
رقم الانضمام: |
edsbas.7B662614 |
قاعدة البيانات: |
BASE |