I am a trained evolutionary biologist and now want to shift gear to biotech doing applied projects.
Therapeutic monoclonal antibody development attracts my attention because antibody maturation is essentially an evolutionary process and can be improved from evolutionary point of view, such as increasing the efficiency in exploring the adaptive landscape.
I wonder what are the bottlenecks: say if antibodies produced by current methods routinely achieve high enough affinity already to the target antigens while it is the downstream in vivo tests in animal/humans where things tend to fail, then my expertise in evolution is useless to the field.
There are many, of course. One you allude to, i.e. effectiveness. Is the target a relevant clinical target; does interaction with the target result in efficacy and is this safe? Also, many regulatory barriers, i.e. process takes time and effort, both in the clinic, and will non-human studies, and, importantly, animal studies. Manufacturing is key - how costly/efficient is the process? Can it be validated and qualified? How do you define and release the product for use? Is it stable? What about intellectual property? Is there possibility for a patent to be obtained? I am far from an expert on the chemistry and biology of these molecules, but don't believe that target affinity is the major issue with these products. Good luck with your career choice, whatever it may be.
Your evolutionary background would be most useful in generation of different clones using genetic libraries, or some such technology. David is correct in that generating antibodies that bind the target at appropriate affinities is usually not the bottleneck. Solving all the remaining characteristics such as stability, immunogenicity (anti-antibodies), efficacy, safety, etc. is where the major problems lie.
Binding is not enough, it is easy enough to target a cell surface antigen in a tissue culture dish, but a living organism is a different story.
One problem lies in the expression profiles of the target proteins in the organism: e.g. in tumor targeting, normally the tumor antigen is also expressed, although at lower levels, in other tissues. Also, tumor cells may adapt to the presence of antibodies and antibody drug conjugates by loss of tumor antigen. Antibodies by themselves may block protein-protein interaction, but to eliminate tumor cells, they need to either be able to recruit complement, macrophages or cytotoxic T-cells. Therapeutic antibodies "armed" with cytotoxic agents may also target cells and organs that take up antibodies by antigen-independent mechanisms (eg. liver cells). Also, full size antibody may not be able to penetrate deeply enough into poorly vascularized solid tumors, while smaller molecules, such as single-chain variable domains, are quickly eliminated through renal clearance.