Wistar Scientists Successfully Engineer a Goldilocks Construct: Therapeutic Antibody Could Be a Future Medicine to Improve Outcomes for Melanoma

In recent years, multimodal therapies have emerged as a route to treat cancer by delivering different types of treatments together to improve effectiveness. However, the more modalities there are, the more complex the production and effects of these lifesaving treatments can become.

Wistar researchers have engineered a linked molecule that enables a three-modality therapy for treating melanoma. They accomplished this by connecting a cytokine and an antibody—which would ordinarily be administered separately—and then engineering a form that was pro-inflammatory enough to fight the cancer cells but not so inflammatory as to cause complications or reduce survival outcomes, according to a recently published study in Frontiers in Immunology.

“We took aspects of a cancer treatment regimen and tried to simplify that by combining antibody and cytokine together,” said Nicholas Tursi, the lead author on the study and a graduate student researcher in the lab of Dr. David Weiner, executive vice president, director of the Vaccine & Immunotherapy Center, and W.W. Smith Charitable Trust Distinguished Professor at The Wistar Institute. “I focused on engineering an intermediate cytokine that is efficacious but also has an acceptable pro-inflammatory profile—a Goldilocks approach.”

The engineered “Goldilocks” cytokine Tursi and his colleagues, including Dr. Weiner and Dr. Daniel Kulp, Associate professor in Wistar’s Vaccine & Immunotherapy Center, engineered to test their antibody cytokine chimera was called HL2-KOA1, a modified designer version of the T cell growth factor IL-2. This engineered molecule used in a combination therapeutic regimen was effective at promoting survival in a rigorous melanoma model.

“What this suggests is that we could use other antibodies or cytokines to engineer the immune response to further extend efficacy,” said Tursi. He is hopeful that this research will serve as the foundation for developing other antibody cytokine chimeras that work for melanoma and potentially other cancers.