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Fox Chase Cancer Center Researchers Uncover ONC201 Immune-oncology Effects

March 20, 2018

Wafik El-Deiry MD, PhD, FACPWafik El-Deiry MD, PhD, FACP

PHILADELPHIA (March 20, 2018) – Oncoceutics, Inc. announced today that the Journal of Clinical Investigation recently published a scientific article describing ONC201’s ability to cause intratumoral accumulation and activation of natural killer (NK) and CD3+ T cells in mouse models and patients. The publication is from the laboratory of Wafik El-Deiry MD, PhD, FACP, Scientific Founder of Oncoceutics, and Deputy Cancer Center Director for Translational Research at Fox Chase Cancer Center.

ONC201, founding member of the imipridone class of small molecules that selectively target G-protein coupled receptors (GPCRs), antagonizes dopamine receptor D2 that is expressed on tumor cells and immune cells. ONC201 stimulates the infiltration of activated NK cells into the tumor that further contributes to the overall anti-cancer efficacy along with direct tumor cell kill. Immune activation by ONC201 is consistent with its ability to stimulate downstream TRAIL pathway signaling that is part of the body’s immune surveillance mechanism against cancer. An increase in activated TRAIL-secreting NK cells was observed in the peripheral blood of patients after receiving ONC201 treatment. These results highlight the potential utility for ONC201 in combination with immunotherapy agents such as anti-PD-1 therapy. The article also provides a preclinical rationale for ONC201’s weekly dosing clinical regimen and evidence of an anti-metastatic effect.

“Immune cell activation in the tumor and inhibition of metastasis with an oral, infrequently administered and well tolerated small molecule provides an attractive treatment option for patients. Immune activation is recognized as an important requirement to achieve durable and complete remissions in conjunction with standard-of-care therapies,” said El-Deiry. “We discovered ONC201 through its ability to stimulate TRAIL pathway signaling that now provides a mechanistic explanation for immune cell activation.”    

“The ability to selectively activate NK and T cells through an alternative mechanism is particularly relevant in immune-suppressed tumors such as glioma and provides opportunities for rational combinations with immunotherapy and other treatment modalities such as radiotherapy,” said Varun Prabhu, PhD, Associate Director, Research and Development, at Oncoceutics. “Immune cell activation further explains the durable tumor shrinkage and clinical benefit of ONC201 that has extended beyond 2 years in some glioma patients.”

       

The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.
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