Pinpointing New Allies in the Fight Against Cancer

Siddharth Balachandran, PhD, a co-leader of the Blood Cell Development and Function research program at Fox Chase
Siddharth Balachandran, PhD, is Co-Director of the Center of Immunology at Fox Chase Cancer Center. He and his laboratory team study how cells die during host innate-immune responses to viruses and bacteria, and how to leverage these mechanisms to treat human disease.

Advanced Research Approaches for Immunotherapy

Innovations in cancer treatments start with discoveries in the laboratory – which is where the research expertise at Fox Chase Cancer Center continues to make powerful inroads to care for cancer patients in the local community and throughout the world.

Consider a recent groundbreaking study led by Siddharth Balachandran, PhD, Co-Director of the Center for Immunology at Fox Chase. Dr. Balachandran is driving the development of a much-needed therapy based on discoveries from studying a virus that is very familiar to many people: the influenza virus.

The new therapy is targeted for patients whose cancer is unresponsive to standard immunotherapy. As immunotherapy harnesses the power of the body’s own immune system to attack cancer cells, it can be a game-changer for some, but it is ineffective in up to 80 percent of patients. That’s because many tumors are immunologically silent, or “cold,” meaning they have adopted characteristics that trick the immune system into perceiving them as non-threatening.

Working as part of a collaborative international team, Dr. Balachandran and his fellow researchers knew that finding a way to turn those “cold” tumors “hot” would re-enable the body’s immune system to fight the tumor and rekindle responsiveness to immunotherapy.

“The main problem for patients who do not respond to immunotherapy is the immune system doesn’t see the tumor as dangerous enough,” Dr. Balachandran says. “We know influenza viruses trigger very potent immune responses in infected cells. The entire immune system rushes to the site of infection and quickly eradicates those cells. So we thought: What if we could find a way to mimic a virus infection within a tumor that was otherwise cold? That way, the body’s immune system could fight the tumor as if it were virally infected tissue.”

Driving New Hope and Options for Patients

Dr. Balachandran and his colleagues identified a particular compound called CBL0137 that mimics the flu virus and can trigger necroptosis, a highly inflammatory form of cell death within tumors. In mouse models of melanoma, injections of the compound caused an antiviral response within the tumor mass and alerted the immune system to its presence. This induced necroptosis in cancer-associated fibroblasts, turning the tumor “hot,” and reversed unresponsiveness to immune-checkpoint blockade therapies.

“This is an important study for patients who have failed first-line immunotherapy, because combining a ‘virus mimetic’ immune adjuvant with immunotherapy offers the opportunity to rekindle an immune response and make immunotherapy effective in otherwise unresponsive patients,” Dr. Balachandran says.

The CBL0137 compound is already in clinical trials as a standard chemotherapeutic, so researchers know it is safe and have a solid understanding of its dosing. Dr. Balachandran says that’s key because there is typically a multi-year gap between discovering a compound and using it in patients.

“In this case, we can bypass that wait and get the compound directly into patients for combinatorial use with immunotherapy,” he says.

The results of the study, which was published in the prestigious journal Nature with Dr. Balachandran as a lead author, have led Fox Chase clinicians to begin recruiting for a phase 1 clinical trial in which CBL0137 will be used alongside immunotherapy drugs for immune-relapsed melanoma patients – potentially changing the face of treatment for that cancer.

The Benefits of Research at Fox Chase

Research like this aligns with the focus of Dr. Balachandran’s Fox Chase laboratory team, which primarily studies how cells die during host innate-immune responses to viruses and bacteria, and how to leverage these mechanisms for the treatment of human disease. Dr. Balachandran says this kind of innovative research is possible at Fox Chase because they have the gift of time and the freedom to explore.

“The only resource we need, other than the money to do our science, is breathing space,” he says. “More and more, funders and hospitals want scientists to take the shotgun approach of finding new cancer therapeutics. But it doesn’t work like that. Many of the major discoveries that have produced important therapies have come from serendipitous findings by individual laboratories, typically when studying something else. Science doesn’t work in this linear way that people think it does — It’s a lot more zig-zaggy.”

That’s exactly what happened when Dr. Balachandran’s international team used research from a completely different area — influenza — to uncover new information about cellular immune responses that scientists were then able to apply to cancer therapy for direct benefit to patients. He says that wouldn’t have been possible just anywhere.

“Fox Chase trusts in our ability as scientists to make discoveries,” Dr. Balachandran says. “They allow us to do any research we want. If they restricted our studies just to areas considered ‘cancer relevant,’ this discovery wouldn’t have ever happened.”

Research, Care, Community

With a long and storied history of breakthrough research, Fox Chase continues to lead the field with seminal scientific discoveries that have key translational implications. The insights gleaned from our laboratory studies can be directly applied to patient care while safely evaluating new approaches to preventing and treating cancer through clinical trials, which may eventually drive standard protocols with far-reaching implications.

That’s the benefit of Fox Chase’s elite standing as an NCI-designated Cancer Center: Our research is led by extraordinarily talented scientists who work in an ideal environment for fundamentally important discoveries. With additional support from our partnership with Temple University Health System’s oncology research, treatment and prevention programs, Fox Chase research makes a world of difference in Northeast Philadelphia and all other communities that we serve.

Become Part of Tomorrow’s Cancer Care Today

As one of the four original cancer centers to receive comprehensive designation from the National Cancer Institute, Fox Chase Cancer Center has been at the forefront of cancer research for more than 100 years. With a singular focus on cancer, we combine discovery science with state-of-the-art clinical care and population health.

Interested in joining our world-class research team to advance the fight against cancer?

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