Monoclonal antibodies are the most used immunotherapy method for various diseases such as cancer and infections. With immunotherapy, mAbs’ ability of binding specifically to certain proteins or cells is exploited to boost the immune system against diseased cells.
The first FDA approved mAb drug, Muromonab, was developed to specifically bind to the CD3 receptor on the surface of human T cells to prevent T cell-driven acute rejection in patients with organ transplants1. To date, the FDA has approved 100 mAb drugs that have a wide range of cellular targets such as PD1/PDL1, HER2, and EGFR2.
To treat diseases at the clinic, mAbs can remain canonical, or be engineered into different formats (e.g., conjugated, bispecific, fragments mAbs, etc. – see Figure 1)2. Depending on their configuration, mAb drugs work differently per treatment. A typical canonical mAb usually works by binding to an antigen (i.e., on a pathogen or an antigen-presenting cell) to trigger an immune response to destroy the pathogen or cell. Engineered mAbs such as conjugated mAbs are coupled to a small molecule drug or radioactive element3, so that they may deliver these drugs, or elements4, directly to cancer cells, like a trojan horse5. Another type of engineered mAbs – bispecifics – is used as a “bridge” to simultaneously target two cellular receptors on a cancer cell and a cytotoxic T lymphocyte to orchestrate targeted cancer cell death5,6.
Figure 1. Infographic illustrating types of monoclonal antibodies. Therapeutic antibodies are typically engineered off an IgG backbone. Though they used to simply involve chimeras, or humanized antibodies7, monoclonal antibodies now include a range of formats, including proteolysis-targeting chimeras (PROTACs)-conjugated antibodies8, antibody micelles9, antibody-cytokine fusion proteins10, trispecifics and many more4.