PHILADELPHIA, PA — The Wistar Institute, led by Dr. David B. Weiner, has announced successful preclinical tests of a groundbreaking immune therapy for glioblastoma, a highly aggressive brain cancer with limited treatment options. The study, recently published in the Journal for ImmunoTherapy of Cancer, reveals promising potential for improving survival rates and reducing tumor burden in preclinical models.
Glioblastoma, known for its extreme diversity and natural resistance to immune attacks, is one of the deadliest brain cancers, with a five-year survival rate of under 5%. These challenges make it notoriously difficult to treat with traditional or immune-based therapies.
Dr. Weiner’s team developed an innovative therapy featuring a DNA-encoded trispecific antibody system, called “DTriTE.” This unique approach links cancer-killing T cells to two specific antigens found on glioblastoma tumors—IL-13Rα2 and EGFRvIII—allowing the immune system to identify and attack cancer more effectively. The therapy’s trispecific design provides greater flexibility in targeting the variable nature of glioblastoma tumors by addressing both antigens simultaneously.
“Our novel trispecific antibody design targets glioblastoma with precision, aiming to limit the tumor’s ability to escape immune responses,” said Dr. Weiner. “We are encouraged by these results and see potential for broader applications in other cancers resistant to existing treatments.”
Testing in preclinical models showed remarkable results. The DTriTE not only activated T cells to fight tumors but also engaged Natural Killer (NK) T cells, another key player in the immune response. The leading DTriTE design achieved 100% tumor control and survival in the experimental glioblastoma models during its initial testing. Even in extended studies, where long-term effectiveness was evaluated, 66% of treated models maintained tumor suppression and survival—far surpassing any other approaches tested.
“This technology represents a promising path forward, even for glioblastoma patients who lack effective treatment options today,” said Daniel H. Park, the study’s first author and a Ph.D. student in Dr. Weiner’s lab. “We are excited to further advance this therapy and explore its potential for other challenging cancers.”
While the therapy is in its early development stages, the results suggest it could become a powerful tool in the fight against glioblastoma. Wistar researchers plan to build on these findings and explore further clinical applications, aiming to offer new hope to patients facing this devastating disease.
Dr. Weiner leads the Vaccine & Immunotherapy Center at The Wistar Institute and holds the W.W. Smith Charitable Trust Distinguished Professorship in Cancer Research, supporting ongoing advancements in immune-based cancer treatments.
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