Nanobodies For Targeted Therapy.docx

“Nanobodies for targeted therapy” By Cintia Torres (6324452) Antibodies are glycoproteins that the immune system uses to identify potential threats such as virus or bacteria. The structure of these antibodies usually consists of four polypeptide subunits, being two heavy and two light chains. Each of these heavy and light chains have a constant region (Fc) that serves as structural base and a variable region (Fab) that recognizes and binds to a specific antigen, for instance, certain pieces of a specific virus. The conserved structure of Immunoglobulin G (a kind of human antibody) consists of two identical heavy chains and two identical light chains. However, the Camelidae family (which includes camels, alpacas, llamas and other animals) have an additional type of IgG, that in contrast to that found in humans, only consists of two heavy chains. The variable domain of the heavy chain was identified as the smallest fully functional portion that would produce the binding of the antigen (1). That small fragment was called a “nanobody”’. Nanobodies are able to bind to transmembrane protein receptors that can be used, for instance, as cancer targets when the receptors are growth factors such as EGFR1 and EGRF2. Mutations on those two growth factors are a main element to develop cancerous cells. Targeted therapy seeks to send medicines to the specific place in the body where it is needed. Since antibodies serve as natural messengers, they are used as binder for those molecules. However, the construction of said targeted system needs other elements apart from the binder (nanobody) and the medicine. A biomarker (surface protein specific for cancer cell) should be identified and a linker should be used to complete the messaging system. One advantage of this kind of drug delivery is that it is highly specific, thus reducing many possible side effects for the therapy. However, one of the main disadvantages and the challenge that the researchers face is that the nanobodies can lose their binding properties when they conjugate to an effector domain (for instance, in the effector Fc region) (1). The obtention in llamas of said nanobodies and the characterization and identification of anti-EGRF activity and their different applications in medicine were discussed by Dr. Paul van Bergen en Henegouwen. The answer to the research question: is it possible to use nanobodies for the targeted delivery of drugs? Is still ongoing, however it is already showing promising results, for instance, in the delivery of trastuzumab in animal models. References (1) Kijanka, M., Dorresteijn, B., Oliveira, S., & van Bergen en Henegouwen, P. (2015). Nanobodybased cancer therapy of solid tumors. Nanomedicine, 10(1), 161-174. doi: 10.2217/nnm.14.178