Korean Biotech, AbClon Enters Trials with New CAR-T Molecule against Ovarian Cancer
Chimeric Antigen Receptor T-Cell (CAR-T) immunotherapy has revolutionized the treatment prospects for hematopoietic malignancies, with two FDA approved products and many others in clinical trials. This adoptive cell therapy is a unique form of treatment wherein T-cells obtained from the patient are genetically modified and reinfused back into the bloodstream to destroy the tumor cells. However, its achievements in treating blood cancers have not yet translated to solid tumors due to the lack of specific antigen targets. Only last year, a CAR-T targeting the MUC1 transmembrane cleavage product entered the first-in-human trials for solid tumors. The therapy also has some limitations, the major one being the toxicity that is caused when administered. South Korean firm AbClon, has developed a switchable, new CAR-T molecule through its antibody platform that could solve some of these pitfalls.
The zCAR-T Platform
AbClon is an antibody engineering biotech company launched in 2010. It has developed zCAR-T, a platform for optimizing new generation CAR-T cells, which when administrated alone, would elicit no responses. These cells have cotinine as a switchable-hapten serving as a controllable link between tumor-specific antigen and the CAR-T cell. This “switchable modulator” helps the T cell to recognize and enable the attack signaling. The new generation CAR-T could be used for multi-targeting and its toxicity could also be modulated by terminating the recognition process. A whole library comprising of a variety of antigen-modulator molecules enabled fast screening without engineering the CAR-T cell for different antigens every time. With their antigen library, the company has already offered to help the government in discovering an antibody treatment for the COVID-19 pandemic. Twenty possible molecules were chosen to be tested for their efficacy in combating the new coronavirus.
AT501 Removes Ovarian Tumor with Single-Dose Treatments in Mouse Models
The company has now announced preclinical results of its novel anti-cancer drug candidate AT501, identified through its zCAR-T platform. AT501 fully diminished ovarian cancer cells in mouse models after just one treatment in 14 days. AbClon says that the preliminary trials of AT501 will be launched in the first half of 2021. This is AbClon’s first attempt to conquer solid tumors with its new generation CAR-T therapy. The switchable CAR-T cells might benefit patients with better precision and less adverse effects while removing the solid, highly heterogeneous malignancies. The firm wishes to expand its treatments to more solid tumors such as pancreatic and colon cancer, following positive safety and efficacy studies.