DNA-delivered immunotherapy shows promise for ovarian cancer

Researchers at The Wistar Institute have developed a DNA-delivered immunotherapy that could improve the treatment of ovarian cancer by overcoming key limitations of current bispecific T-cell engager (BTE) therapies. The findings [1] have been published in Molecular Therapy.

BTEs have transformed the treatment of certain blood cancers by directing the body's T cells to attack tumour cells. However, their success against solid tumours has been limited due to their short lifespan in the body and the complex nature of solid cancers.

The Wistar team has addressed these challenges by creating a novel DNA-based delivery platform that enables the body to produce BTEs directly within muscle tissue. Incorporating an innovative 'knob-into-hole' antibody design, the approach enables complex therapeutic molecules to assemble accurately in vivo while prolonging their therapeutic activity in the body.

"Showing that we can deliver these really complex molecules in vivo was a very exciting achievement that demonstrates its potential as a next-generation tool to improve patient outcomes," said Pratik S. Bhojnagarwala, PhD, postdoctoral fellow at The Wistar Institute and first author of the study. "The body's muscle cells keep producing it, instead of patients having to return for multiple doses."

In preclinical studies, the DNA-delivered BTEs slowed ovarian tumour growth more effectively than conventional approaches. The researchers also demonstrated that two different BTEs could be delivered simultaneously, enabling the therapy to target multiple tumour antigens and helping to overcome one of the key mechanisms of treatment resistance.

The platform also offers practical advantages beyond improved efficacy. Because the therapy is delivered as DNA, it has the potential to simplify manufacturing, reduce costs, eliminate cold-chain storage requirements and decrease the number of treatments required, as patients' own muscle cells continue producing the therapeutic proteins.

Laboratory studies using human ovarian cancer cells also showed encouraging results, while combining the treatment with immune checkpoint inhibitors further enhanced anti-tumour activity.

The researchers believe the platform could provide a next-generation approach to treating ovarian cancer and other solid tumours. Future studies will evaluate the therapy in more advanced preclinical models before progressing towards human trials.

More information online

1. Efficient in vivo assembly of DNA encoded multivalent BTEs for dual antigen targeting for broadening therapeutic impact in ovarian cancer.published in Molecular Therapy, 2026. Online publication