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Kuala Lumpur: Even with new immunotherapies, only around one in 10 patients ultimately survive from advanced clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer with few treatment options.

Currently, The Wistar Institute scientists have built upon bispecific T cell engagers (BTEs) technology to develop new and improved recombinant and synthetic DNA versions of therapeutic antibodies that target CA9, called Persistent Multivalent T Cell Engager (CA9-PMTE) that shows promise in pre-clinical models as a potent, long-lasting treatment against ccRCC.

While BTEs are a promising new antibody therapy for many difficult-to-treat cancers, they do have some limitations, including a short half-life, with most BTE drugs break down quickly, sometimes within a matter of hours, which means they are only effective for a short time.

Senior author David Weiner, who is also the executive vice president of The Wistar Institute and director of the Vaccine & Immunotherapy Centre, said the new format represents the potential for an important new tool for enhancing cancer therapy.

According to a statement, in this study, the researchers also demonstrated that the more potent therapy could be delivered using synthetic DNA, allowing therapeutic production directly in patients.

In preclinical models, the team tested the efficacy of novelly designed anti-ccRCC BTE variants developed to enhance the interactions between T cells and the targeted cancer.

These were developed to be delivered using synthetic DNA technology.

The researchers compared traditional BTEs with a newer format design termed persistent BTEs (PBTEs), which have a longer half-life but use the same targeting system as older BTEs and found that, while the initial PBTEs did last longer than the traditional BTEs, the new design reduced the overall anticancer potency.

The research team then created a new molecule by taking an existing PBTE and adding additional binding domains to better “see” and bind to the cancer, whereby this novel, alternative design, called a persistent multivalent T cell engager (PMTE), proved to be highly potent while also maintaining a longer half-life than the traditional BTE design.

The researchers are now studying these new PMTEs in combination with other immunotherapies as well as expanding designs to additional difficult-to-treat cancers.