[대학원 생명과학과 세미나 안내]
연사 : Magez Stefan 교수(Ghent Univ. Global Campus)
연제 : Structural and Functional ImmunoParasitology; Nanobody screening and semi high-throughput image processing
일시 : 2016년 10월 21일 (금) 오후 4시
장소 : 하나과학관 A동 109호
초청교수 : 최무현 교수
Abstract
Nanobodies are small recombinant antibody fragments that are produced using the coding sequence of the minimal binding domain of a camelid single-chain antibody. The size of a nanobody is about 10 times smaller than a conventional antibody, which allows it to be used in various novel antibody-based technologies.
One problem often encountered in the design of immunodiagnostic tools for infectious agents is the fact that the infecting organism itself is inducing host antibodies. Hence, detection of pathogen released or secreted molecules can subsequently only be done if diagnostic antibodies can somehow be raised that are ‘better’ than the host antibodies, and that can outcompete the latter when immune complexes are formed. This result is very hard to obtain with conventional antibodies as they are targeting their epitopes in a similar manner as would infection-induced host antibodies do. Using nanobodies allows circumventing this issue. Indeed, as single-chain antibodies are forced to interact with their epitopes in a different way as compared to conventional VH-VL antibodies, this characteristic can be used to circumvent competition.
At our laboratory at the Vrije Universiteit Brussels (VUB) we have more than 20 years of experience with nanobody technology, as we were the first to discover and fully describe single-chain camelid antibodies, and were subsequently capable of turning this discovery into a biotechnological application. At the Laboratory for Cellular and Molecular Immunology (CMIM) we have been involved in the generation of nanobodies for use in future diagnostic tools as well as their use in other medical interventions. At the Unit for Structural and Functional Immunoparasitology that is part of the CMIM laboratory, the main research target is the parasitic infectious disease called ‘trypanosomosis’. While this infection if often associated to Sub-Sahara Africa, trypanosomisis is actually a disease that also affects Asia, South America and Europe. Indeed, animal infections with various trypanosomes are rapidly spreading throughout the world and little attention is given to date to stop this infection, despite its huge economic impact. The main problem with the disease is that there are virtually no flied-applicable diagnostic tools available, with the exception of an antibody screening test for Human African Trypanosomiasis in West-Africa. PCR and other molecular tools exist, and can be performed in well-equipped laboratories, but these techniques are unsuitable for rural field use. The main issue at hand preventing functional diagnostic kits seems to be the fact that trypanosomes have a very profound impact on the B-cell biology of the host, inducing a state of polyclonal B-cell activation, which interferes as outlined above with the development of any antibody-competing assay for target molecules. Antibody testing itself has its own drawbacks as this technique cannot differentiate between an active infection and a past cured infection (which is a huge problem for any antibody-based diagnostic test for any disease). Hence, at CMIM we are now combining our vast knowledge of trypanosome infections and our knowledge in antibody engineering to develop a new generation of diagnostic antigen test tools, based on nanobody recognition. In the case of trypanosomosis, the development of a nanobody-based dipstick in now in full progress, having overcome technical hurdles such as nanobody-gold labeling and nitrocellose coating.
Besides trypanosomosis, a number of other malignant conditions are now being targeted at CMIM by the use of nanobodies. Tumor targeting as aid in clinical interventions is just one of them, while anti-toxin treatment in case of scorpion stings is another. Together, these research topics show that antibody engineering and nanobody technology are being used to take a whole new approach to antibody-based immune intervention, and that new future applications are plentiful.