Delhi, Feb. 24, 2023 (GLOBE NEWSWIRE) -- Over the years, immune checkpoint inhibition has developed itself as one of the cornerstones in cancer therapy arising from their otherwise detrimental role in cancer. The immunosuppressive environment created because of immune checkpoint proteins harbors an apt environment for the proliferation of cancer cells. Therefore, inhibition of checkpoint proteins has become an essential and emerging strategy for cancer treatment. Post the identification of immune checkpoints, research studies were focused on identifying more immune checkpoints and the B7-H3 was one of those discovered in the early 2000s. The protein has certain properties that make it different from other immune checkpoints, increasing the interest of researchers and drug developers looking for a novel protein to target to treat cancer.
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Targeting of the B7-H3 as a therapeutic strategy makes up for the second generation of immune checkpoint inhibitors, which also includes inhibitors of LAG-3, TIM3 and TIGIT among a few other checkpoint proteins. Though a majority of the functions of the B7-H3 protein in humans is not well defined, its overexpression has been linked to a poor prognosis and lower survival rate in cancers like head and neck cancers and laryngeal cancer. As an immune checkpoint, B7-H3 not only regulates the innate and adaptive immunities but also appears to influence the aggressiveness of cancer cells by interacting with a number of receptors, which remain largely unknown. Therefore, targeting B7-H3 has emerged as a promising strategy to for cancer treatment.
B7-H3-expressing cells have been targeted and eliminated using a variety of immunotherapeutic strategies, some of which are currently undergoing human clinical trials. Nonetheless, there are numerous T cell therapies that target the B7-H3 protein in clinical studies, with CAR-T therapies predominating in this field. CAR-T cells, which include chimeric antigen receptors (CARs) engineered to recognize the tumor antigen B7-H3, can specifically target cancer cells that express B7-H3, reducing the risk of unfavorable consequences from off-target interactions.
In addition to dominating the clinical trial landscape for B7-H3-targeted pharmaceuticals globally, China is also dominating the field for B7-H3-directed CAR-T therapies, with a number of pharmaceutical firms, cancer research organizations, academic institutions, and hospitals organising clinical trials for these CAR-T cell candidates. BoYuan RunSheng Pharma, IIT MediTech, PersonGen, Beijing Tiantan Hospital and Shenzhen Children's Hospital are some organizations that have been developing and carrying out clinical trials for CAR-T therapies in China.
To target the B7-H3, antibodies are also being developed in addition to T cell treatments. Clinical trials have gone the furthest with I131-Omburtamab, and it has a unique mode of action. By generating radiation that can lead to cancer cell alterations, the drug's radioisotope can trigger cell death in cancer cells that express the B7-H3. Another contender is Vobramitamab duocarmazine, which combines Vobramitamab, an antibody that targets the B7-H3, and duocarmazine, a chemotherapeutic agent that can cause tumour cell death by altering the nucleic acid sequence.
As a result, a large number of compounds with distinctive cancer cell killing mechanisms have been added to the pipeline as B7-H3-targeting drugs. B7-H3 is a novel immunological checkpoint, and since its receptors are still unknown, it has been difficult to inhibit its interactions with those receptors and, consequently, its signaling pathways. The use of creative cell killing methods by medication makers has allowed them to overcome this issue thanks to their years of drug development knowledge and technological developments. The same is likely to happen in the upcoming years as immune checkpoint inhibition continues to gain notoriety by piquing drug developers' attention. Numerous variables are promoting the B7-H3 inhibitors' development and market potential, and it is anticipated that the first B7-H3 inhibitor will spur more research and development of medications that target this protein.
