Scientists at the Wistar Institute have developed a new type of bispecific T cell engager (BTE) that is effective against ovarian cancer in preclinical studies. It is a major development for this class of immunotherapy, which has been used successfully against blood cancers but has so far been less effective in treating solid tumors.
Bispecific T cell engagers work by simultaneously binding to two targets — one on a T cell and one on a cancer cell — effectively forcing the immune system to recognize and attack the malignancy. The challenge with solid tumors has been the complex tumor microenvironment, which can suppress immune activity and make it difficult for therapeutic molecules to penetrate and persist. The new BTE developed at Wistar overcomes this by being delivered as a DNA molecule that instructs the body's own cells to produce the engager protein continuously, rather than injecting a pre-made protein that degrades quickly.
In preclinical experiments, the DNA-delivered BTE demonstrated potent anti-tumor activity against ovarian cancer cells, showing significant tumor regression with a favorable safety profile. The therapy was designed to target specific markers on ovarian cancer cells while minimizing off-target effects on healthy tissues — a critical advantage given that ovarian cancer is often diagnosed at advanced stages when treatment options are limited.
Ovarian cancer is one of the most lethal gynecological malignancies, with a five-year survival rate below 50 percent for advanced cases. The ability to generate a sustained immune response through a single DNA administration could represent a significant step forward in making immunotherapies practical for solid tumors. The Wistar team is now working toward advancing this therapy into clinical trials to evaluate its safety and efficacy in human patients.
Knowledge takeaway: A DNA-delivered bispecific T cell engager developed at the Wistar Institute has shown potent activity against ovarian cancer in preclinical models, potentially opening the door for effective immunotherapy against solid tumors that have historically resisted this treatment approach.