Wistar scientists have developed a new type of bispecific T cell engager, or BTE, that has shown effectiveness against ovarian cancer in preclinical studies. This development marks a significant step for immunotherapy, which has been successful against blood cancers but less effective so far in treating solid tumors such as ovarian cancer, according to a July 21 announcement.
The research team created a novel "knob-into-hole" platform to deliver BTEs. In this approach, an antibody "knob" is engineered to fit precisely with an antibody "hole," resulting in two components locking together like puzzle pieces. The scientists demonstrated that these BTEs could be delivered using DNA-based technology, which may lower manufacturing costs and reduce the treatment burden on patients. Additionally, they developed a method to deliver two different antigen-targeting BTEs within a single dose—a strategy aimed at overcoming therapeutic resistance.
"I think it's a major advancement for the field of bispecific antibodies," said Pratik S. Bhojnagarwala, Ph.D., postdoctoral fellow at The Wistar Institute's Vaccine and Immunotherapy Center and first author of the study. "It's also significant for ovarian cancer, where there's a real need for new therapeutic options, but there are likely broader applications for other solid tumors as well."
Bispecific T cell engagers work by bringing together cancer cells and disease-fighting T cells so that the immune system can target and destroy the tumor cells more effectively. While their use has increased over the past decade in clinical settings—especially against blood cancers—their impact on solid tumors has been limited due to issues such as short half-life and tumor heterogeneity.
The new technology addresses these challenges by using DNA-based delivery to enable muscle tissue to produce BTEs directly within the body. The knob-into-hole design further extends their half-life compared to previous versions. Bhojnagarwala said this approach is more affordable, easier to manufacture, does not require cold storage, and requires fewer doses while lasting longer.
Preclinical models showed that the new BTE lasted longer in the body and was more effective at slowing tumor growth than earlier versions. Laboratory studies indicated efficacy on human patient-derived ovarian cancer cells and suggested that combining this therapy with immune checkpoint blockade could enhance its effectiveness further.
Researchers plan next to test this therapy in advanced models of human cells, with hopes of progressing toward human trials and exploring its application against other types of cancer.
