Despite the availability of innovative immunotherapies, only around one in ten patients with advanced clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer, ultimately survive. The Persistent Multivalent T Cell Engager (CA9-PMTE), which targets CA9, is a new and improved recombinant and synthetic DNA version of therapeutic antibodies that show promise in preclinical models as a potent, long-lasting treatment against ccRCC. To create a new form of treatment, Wistar researchers expanded on the technology of bispecific T cell engagers (BTEs).
Though BTEs are a potential new treatment for many malignancies that are challenging to treat, they do have certain drawbacks, such as a short half-life. The majority of BTE medications degrade rapidly—sometimes in a couple of hours.
The researchers evaluated the effectiveness of newly created anti-ccRCC BTE variants created to improve the interactions between T cells and the targeted malignancy in preclinical models. It was created with synthetic DNA delivery in mind. The researchers compared PBTEs to normal BTEs and found that they used the same targeting technique, albeit with a longer half-life, as older BTEs.
In order to better “see” and bind to the cancer, the research team then used an already-existing PBTE and added more binding domains to create a new molecule. The unique formulation, known as a persistent multivalent T cell engager (PMTE), outperformed the conventional BTE design in terms of potency and half-life.
Director of the Vaccine & Immunotherapy Center and senior author David Weiner, PhD, stated that “bispecifics in general are an important technology that offers significant advantages in on-target anticancer potency.” We have reason to believe that the new PMTEs require a much lower dose and, additionally, a lower frequency of therapy—which could potentially translate to better outcomes and a better patient experience at a lower cost—in addition to appearing more effective at binding to tumor cells and killing the cancer.
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