The success of the field of oncology immunotherapy is built on the foundation of effective and long-lasting immune responses. Moreover, the global incidence of cancer is increasing year by year, and because various tumor cells also express CD137, researchers have been striving to understand its distribution in order to discover potential therapeutic effects or adverse reactions. Although the expression of CD137, also known as 4-1BB, and its functional role in immune cells have been extensively studied, significant areas remain to be explored. Several in vitro studies have documented the expression of CD137 in various cancer types, including leukemia, lymphoma, and other malignancies. While numerous studies exist, they are primarily conducted on mouse models, and some have progressed to clinical testing.
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The revitalization of cancer immunotherapy with the emergence of various immunomodulatory checkpoints, such as the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1), has led to the identification of additional checkpoints and immunostimulatory strategies. One significant discovery is that of the CD137 molecule, a member of the co-stimulatory tumor necrosis factor (TNF) receptor superfamily. Preliminary studies have indicated that CD137 is involved in tumor growth suppression, as demonstrated in murine models.
As a result, multiple researchers and academicians are focused on developing anti-CD137 antibodies to inhibit tumor cell growth. Consequently, several clinical studies are ongoing in this area. For example, a novel candidate called ADG206 is currently being investigated bng its developer Adagene in a phase 1 clinical trial for the treatment of patients with advanced or metastatic solid tumors. Moreover, Adagene has used its NEObodyTM platform to create ADG106, a ligand-blocking fully human agonistic anti-C D137 IgG4 monoclonal antibody. ADG106 is being tested in early phase clinical trials to treat patients with non-Hodgkin's lymphoma and/or advanced solid tumors.
The pipeline for CD137-targeted immunotherapy is steadily expanding, with over 60 new candidates being added. There is a pressing need to enhance treatment options for cancer patients. Consequently, CD137 antibodies are frequently combined with other drugs to improve their effectiveness. For example, the novel candidate LVGN6051 is currently undergoing clinical trials in combination with Pembrolizumab for metastatic cancer patients, Anlotinib for those with soft tissue sarcoma, toripalimab and paclitaxel for head and neck squamous cell carcinoma, and nab-paclitaxel or bevacizumab along with cyclophosphamide for metastatic solid tumors.
The involvement of major pharmaceutical companies such as Pfizer and Bristol Myers Squibb has attracted various other pharmaceutical collaborations, hospitals, and research centers, including the University of Southern California Norris Comprehensive Cancer Center, Ashford Cancer Center Research, and the Cancer Hospital of the Chinese Academy of Medical Sciences, all targeting multiple cancer disorders. These examples illustrate the maturing market for CD137-targeted immunotherapy worldwide.
While some anti-CD137 antibodies have advanced to phase 2 clinical trials, several side effects, including liver inflammation, have been reported. To tackle these issues, next-generation CD137-targeting antibodies, such as FS-222, are being developed. FS-222 is a tetravalent, bispecific antibody that targets both CD137 and PD-L1, and it is being developed by F-star Therapeutics for the treatment of solid tumors. This candidate is created using F-star's Modular Antibody Technology platform and is designed to be used as part of a combination therapy.
As a result of these ongoing advancements, the market for anti-CD137 therapies is growing each year and is expected to further mature as more treatments gain approval in the global commercial market. Factors such as the increasing prevalence of cancer, which is projected to rise significantly in the coming years, alongside continuous research and development efforts in this field, are also driving changes in the global commercial landscape.
