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Researchers Study Protein to Improve Immunotherapy Outcomes for AML

Published on April 16, 2020 in Cornerstone Blog · Last updated 3 years 9 months ago


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Ian Henrich, PhD, and Margaret Chou, PhD, are investigating the effects of USP6, a protein that optimizes a patient’s immune response, on acute myeloid leukemia.

droseyb [at] (By Barbara Drosey)

Even great trees begin as seedlings that require sunlight, water, and nurturing to develop. Groundbreaking science is no different. An idea needs collaboration, resources, and funding support to take root and spread into a concept, a treatment, and sometimes even a cure. The University Science Center QED Proof-of-Concept Program gives roots to early-stage life science and healthcare technologies by providing academic researchers with mentoring, business advice, and funding.

Ian Henrich, PhD, a postdoctoral researcher in the Department of Pathology and Laboratory Medicine at Children’s Hospital of Philadelphia, is one of three researchers selected for this year’s QED program award. In collaboration with Margaret Chou, PhD, a cancer researcher at CHOP Research Institute, Dr. Henrich is investigating a protein called USP6 that rallies a patient's immune system against cancer cells. The team will use the $200,000 grant award to delve into the effects of USP6 on acute myeloid leukemia (AML), the second most common blood cancer.

At the end of the one-year QED period, Drs. Chou and Henrich aim to have a final phase product, a nanoparticle delivering USP6 that can be targeted to the AML cancer cell with verified activity in animal models that will lead to future clinical trials.

“This award allows us to fast track this investigative process to reach patients as quickly as possible,” Dr. Henrich said.

An Unexpected Discovery

Dr. Chou’s lab is focused on understanding pediatric cancer, and the team’s work veered unexpectedly into the field of immunotherapy while investigating USP6.

“We were studying benign tumors and wondered: Why does one tumor remain benign and another progress to full blown cancer?” said Dr. Chou, who is also associate professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania. “Dr. Henrich discovered that this protein we work on, USP6, has potent and multifactorial effects on the immune system. With his initiative and foresight, we decided the logical next step is to develop the protein into a therapeutic.”

While immunotherapy has revolutionized cancer treatment in recent years, currently available immunotherapies target a limited number of pathways that in some cases can lead to the cancer becoming therapy resistant and the patient’s condition progressing.

“What makes our proposed therapy unique is that it simultaneously targets multiple pathways, attacking cancer cells from various immunostimulatory angles, which helps prevent them from building resistance,” Dr. Henrich said. “This novel discovery makes USP6 a first-in-class therapy with the potential to have broader impact on treatment of a variety of cancers than other immunotherapies.”

To understand how USP6 effectively targets cancer cells, Dr. Chou suggests considering the body’s immune system as the military with different modes of attack, similar to the U.S. Army, Navy, Air Force, and Marines. Existing immunotherapies are able to activate one branch of the military. For example, if the Navy is deployed but the ships are blocked from reaching their destination, that offensive, or therapy, will be ineffective. USP6 activates all branches of the immune system’s “military.” So, even if one branch of defense gets blocked by the enemy – cancer – USP6 enables the immune system to engage its forces and attack from other angles.

“It’s the multifaceted function that makes USP6 so special,” Dr. Chou said.

Broad Implications

The researchers are confident USP6-related therapy will have implications beyond AML, based on evidence of its activity in animal models for cancers such a Ewing sarcoma, a particularly insidious pediatric cancer, as well as pancreatic, ovarian, and cervical cancers in adults.

“Not only do we envision that the USP6 nanoparticle therapy could act as the standalone agent in combating cancer, we think it can greatly increase the number of patients who can respond to existing immunotherapies,” Dr. Chou said.

The Chou Lab has been researching this protein for nearly two decades, and find themselves in a unique position; while USP6 was first identified in 1992, it is notoriously difficult to work with, and the scientific literature has yet to describe its immunostimulatory properties. Dr. Chou and her colleagues will soon publish about their work, and anticipate much more to share in the near future.

Read the CHOP press release for more information on USP6.