Personalized Cancer Immunotherapy
Monoclonal antibodies in personalized cancer immunotherapy
Cancer immunotherapy has become a promising treatment for many forms of cancer. It works by improving the functions of the body’s natural defense line – the immune system – to fight cancer. There are currently four forms of immunotherapy, including cytokine therapy, cellular therapy, antibody therapy, and therapeutic vaccines. Among these therapies, antibody therapy is emerging as one of the most promising forms.
PD-1 is a protein found on the surface of T cells. Upon binding with its ligand PD-L1, PD-1 will inhibit T-cell activity and downregulate the immune function. While PD-1 activation may be beneficial in cases of autoimmune disease, excessive activation is proven to be associated with increased tumour aggressiveness and risk of death in cancer patients. Many checkpoint inhibitors targeting PD-1 and PD-L1 have been developed as immunotherapies against various types of cancer, such as melanoma, cervical cancer, non-small cell lung cancer, and head and neck cancer.
Anogen-Yes Biotech believes that treating cancer with checkpoint inhibitors would be more effective if personalized to each patient. PD-1 and PD-L1 consist of 268 and 290 amino acids respectively. This implies that they have dozens of potential epitopes for mAbs to bind with. A single monoclonal antibody can only bind to one epitope due to its specificity. Therefore, one monoclonal antibody alone may not be sufficient in treatment, and the effectiveness varies from patient to patient, depending on the expression levels of PD-1 and probably the exposure of proper epitope.
To tackle this issue, Anogen has successfully generated several dozens of high-affinity monoclonal antibodies (mAbs) that can bind with different epitopes of PD-1 and PD-L1. These mAbs are currently under pre-clinical study and humanization. Using these mAbs clones, Anogen is developing a novel personalized cancer treatment. Before prescribing a checkpoint inhibitor, a companion diagnostic is taken to identify whether the patient could benefit from a particular antibody-drug by screening the existing antibody clones for the patient and finding out the one with the highest therapeutic potential, and then providing targeted and personalized treatment by using the selected antibody. This novel personalized cancer treatment is expected to increase the effectiveness, safety, and efficiency.
CD47 is a transmembrane protein that is expressed by multiple human tumor types. It binds to signal-regulatory protein alpha (SIRPα) on macrophages to send a “don’t eat me” signal to avoid phagocytosis of cancer cells. Blocking CD47-SIRPα interaction is being evaluated as anti-cancer immunotherapy and promising results have been found in several clinical studies. Anogen has developed more than 20 mAbs against CD47. Three clones (8H7, 9F10, and 6A7) have shown excellent effectiveness in inhibiting CD47-SIRPα binding, suggesting that these mAbs have potential for application in cancer treatment after humanization.