As with anything, there are many obstacles that scientists must face in the production and delivery of antibody-based therapies. One of the biggest of these hindrances is protein instability. Differential scanning fluorimetry is one of the most efficient screening methods used to identify low-molecular-weight ligands, which in turn exposes protein unfolding.
An antibody (Ab), also known as an immunoglobulin (Ig), is a protein that forms part of our immune system. They can be classified based on their properties, structure, and function in different varieties known as isotypes. There are five antibody isotypes: IgA, IgD, IgE, IgG, and IgM that target antigens (molecules capable of inducing an immune response). An antibody’s main function is to neutralize pathogens (bacteria and viruses) that we are constantly exposed to in our everyday lives. So, it should come as no surprise that antibodies are used to develop therapeutic drugs for cancer treatment.
Cancer Treatment With mAbs
Monoclonal antibodies (mAbs) are a type of biological therapy used extensively in cancer treatment. Each mAb is produced in a lab and contains multiple copies of one specific type of antibody. MAbs can target and eliminate cancer cells by binding to tumor-associated antigens and triggering the immune effector mechanisms towards the cancer cells. They are very specific molecules in their action against antigens and are able to respond to tumor angiogenesis by inhibiting or stopping tumor growth. Additionally, they can target inhibitory immunologic signals that enhance the anti-cancer cellular immune response.
Anti-cancer mAbs function by using a variety of mechanisms. They can directly target the malignant cells, modify the host response or immunity in response to infection, or deliver cytotoxic moieties to the cancerous cells. In order to achieve these functions each mAb must focus on one specific protein, which means that different monoclonal antibodies must be made to target specific types of cancer.
Efficacy of the mAbs in cancer treatment can depend on many factors. These include protein stability, antigen specificity, overall structure and folding of the targeted protein, affinity for the antigen, and the way the mAb responds as a component of a network that can lead to the apoptosis of the infected cell.
Protein Structure In mAbs
Recent studies have focused on understanding the expression of immunoglobulins like IgG in several cancers. IgGs are naturally-occurring proteins that are well tolerated by the host, when used as mAb therapeutic agents. They have the ability to bind to specific parts of cancer causing antigens, and their long half-lives and biodistribution are crucial for their clinical effectiveness as they mediate a prolonged anti-cancer response.
Recent analysis of antibody therapeutics circulated in the bloodstream show that over time proteins can have altered physicochemical characteristics and, therefore, lower therapeutic potency (1). New research technologies enable scientists to use nanoDSF that allows for the evaluation of protein stability. By understanding how proteins used in treatments such as mAbs evolve in their host, cancer treatments can be more effectively monitored and developed.
- Jefferis R. Glycosylation of recombinant antibody therapeutics. Biotechnol Prog. 2005;21:11–16.