Antibody production expertise and techniques have grown for the creation of tools for biological research and clinical diagnostics. Methods that use antibodies include ELISA, flow cytometry, immunohistochemistry, immunoprecipitation, and Western Blot. Antibody development is typically achieved by injecting antigen into a small animal (immunization step) or by using phage display methods. The challenges associated with the development of antibodies are typically their specificity, initial quantity produced, and future production required.
A rapidly growing area of antibody development is that of therapeutic monoclonal antibodies, i.e. used in the treatment of diseases. In 2017, 61 mAbs and 11 Fc-Fusions were in clinical trials. These new drugs hold the promise of treating multiple classes of diseases, particularly cancer and chronic inflammation. This class of antibodies faces multiple challenges specific to biomedicines and drug development.
Toxicity
The antibodies initially produced in an animal must be humanized to reduce the immune responses specific to the presence of exogenous constant domains, resulting in recombinant chimeric antibodies. The reference humanization technique is CDR-grafting. Significantly reducing the toxicity of the therapeutic mAbs, a humanitarian response is still observed in about 9% of patients.
Efficacy
Although therapeutic antibodies are successful against diseases with more severe or no treatment, they are subject to internal resistance mechanisms. This results in a loss of attachment to the surface of the target cells, a process called "modulation". To overcome this, constant domain Fc engineering is implemented, resulting in targeted mutations.
Specificity
Because of the detection limits of an antigen, biotech companies have developed bispecific antibodies, i.e., that recognize multiple targets. The advantage of these bispecific antibodies or bispecific antibody fragments is, depending on the strategy, to increase selectivity for a given target cell, or to recruit both target and effector cells.
Production capacity and costs
The production of mAbs is done by expression via immortalized hybridomas. However, the low production yields of these cell lines and the genetic modifications that can be introduced have led to the development of new production models. These methods include the use of mouse ascites (with regulatory limitations in terms of application), and recombinant expression through high production efficiency lines.
