This project is no longer listed in the FindAPhD database
and may not be available.
Over the last decade, monoclonal antibodies (mAbs) have become established as highly effective agents for the treatment of cancer, inflammation, infections, and a range of other conditions. In fact, mAbs are currently one of the fastest growing classes of therapeutic agent. Building on this success, there is a great deal of interest in development of novel and improved mAbs or mAb-based formats designed for new treatment options. In oncology, for example, new mAb formats may offer more potent killing efficiency or target additional types of cancer. One exciting possibility is to fuse enzymes or other partners to a tumour-specific mAb, or a subcomponent of such a mAb, to produce a conjugate that will localize to the tumour site and display novel killing properties.
The project aims to build on our experience in manipulating immunoglobulin genes as a means to dissect antibody function. The objective is to engineer novel mAb conjugates directed aginst tumour-specific markers that have been validated in previous studies. Following expression and purification, the mAb conjugates will be fully characterised in terms of their biochemical properties, their antigen binding specificities and affinities, and their capabilities to mediate tumour cell killing. The project will offer training in a broad range of techniques including DNA manipulation, mammalian cell culture and transfection, biochemical and immunological techniques, molecular interaction analysis in surface plasmon resonance experiments, and cell killing assays. Immersed in a stimulating and supportive environment, the student will also gain insights into commercialisation and intellectual property issues relevant to the development of therapeutic mAb reagents.
Funding Notes:
References:
Weiner L.M. et al. (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat. Rev. Immunol. 10, 317-327.
Woof J.M. and Russell M.W. (2011) Structure and function relationships in IgA. Mucosal Immunol. 4, 590-597.
Balu S., Reljic R., Lewis M.J., Pleass R.J., McIntosh R., van Kooten C., van Egmond M., Challacombe S., Woof J.M. and Ivanyi J. (2011) A novel human IgA monoclonal antibody protects against tuberculosis. J. Immunol. 186, 3113-3119.
Research Assessment Exercise (RAE) 2008 Results