Made in City of Hope: Drug stops cancer’s siren call to the immune system

December 4, 2014 | by City of Hope

Cancer has a way of “talking” to the immune system and corrupting it to work on its own behalf instead of defending the body. Blocking this communication would allow the immune system to see cancer cells for what they are – something to be fought off – and stop them from growing.

Hua Yu, Ph.D, and her lab team At City of Hope, Hua Yu and her team developed a drug that will clamp down on STAT3, halting its ability to talk to the immune system.

A breakthrough

Scientists have known for some time that cancer uses a protein called STAT3 to talk to the immune system. At City of Hope, Hua Yu, Ph.D, the Billy and Audrey L. Wilder Professor in Tumor Immunotherapy, and her team sought more than simply an understanding of how the two are able to connect and communicate. They wanted to create a treatment to address it.

Based on what they discovered about how STAT3 works, Yu and her team developed a drug that would clamp down on STAT3, halting its ability to talk to the immune system. Known as CpG-STAT3 siRNA, the drug administers a dual blow: It blocks the growth of cancer cells, even as it sends a message to surrounding immune cells to destroy the tumor. CpG-STAT3 siRNA also appears to enhance the effectiveness of other immunotherapies, such as T cell therapy, by helping prevent cancer from subverting the immune system.

Promising results

In preclinical studies, CpG-STAT3 siRNA effectively stymied growth of aggressive lymphomas and the brain cancer glioma, two deadly cancers with no current viable therapies. Promising results were also found with CpG-STAT3 siRNA and leukemia.

It could only be made here

In a different setting, the discoveries that Yu and her team made might have remained only that: discoveries. But City of Hope’s translational research model ensured that Yu and her team had the resources, support and expertise they needed to transform science into treatment.

Bringing a new treatment to first-in-human trials is a team effort. Scientific researchers such as Yu cannot work directly with patients: They need to partner with doctors. City of Hope’s collaborative environment enables Yu to work with doctors who are experts in their fields and experienced in clinical trials.

The Center for Biomedicine & Genetics accelerated CpG-STAT3 siRNA’s progress from preclinical trials to first-in-human trials. By having a Food and Drug Administration-compliant manufacturing facility on campus, researchers could cut both production costs and time — and keep the patent for the drug. This ensures that royalties from CpG-STAT3 siRNA will be funneled back into further research at City of Hope.

Moving forward

Yu and her colleagues are preparing to take CpG-STAT3 siRNA to a first-in-human trial for B cell lymphoma and glioma patients. To that end, CpG-STAT3 siRNA is now in production on campus at City of Hope. Pending confirmation of the drug’s safety in the first phase of the trial, it will then be tested in combination with T cell therapy. Researchers across campus are eagerly awaiting the results.

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