On July 08, 2015

Researchers at the University of California, San Diego School of Medicine and Moores Cancer Center are working with GSK on a bench-to-bedside project to treat leukemia and other diseases by eliminating cancer stem cells. The collaboration is part of GSK’s Discovery Partnerships with Academia (DPAc) program, where academic partners become core members of drug-hunting teams. Catriona Jamieson, MD, PhD, associate professor of medicine and chief of the Division of Regenerative Medicine, will lead UC San Diego’s effort in the new DPAc team.

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The UC San Diego-GSK DPAc team will collaborate to discover and develop a new therapeutic compound that inhibits RNA editing, a process cells use to enhance RNA diversity prior to translating genetic information into proteins. Jamieson’s group has shown that uncontrolled RNA editing helps cancer stem cells self-renew, making more malignant cells, in chronic myeloid leukemia and other blood cancers. Cancer stem cells can become dormant and evade chemotherapy and then activate again later, causing relapse of leukemia and other cancers and allowing tumors to resist treatment.

"The problem with leukemia is that in many cases while we can control the symptoms of disease, we can’t completely eradicate it because current therapies don’t block cancer stem cell self-renewal. Enhanced RNA editing is like a cancer stem cell engine, and with this collaboration we want to turn that engine off," said Jamieson, who is also deputy director of the Sanford Stem Cell Clinical Center and director of stem cell research at UC San Diego Moores Cancer Center. "We’re very fortunate to have this opportunity to work completely in step with a highly adept, dynamic company to take the RNA editing target idea from design to delivery of a new therapy that may prevent cancer relapse."

GSK launched DPAc as an independent unit in 2010. DPAc’s goal is to expedite promising basic research into drug discovery and development, with the potential to bring innovative new treatments to patients. Each selected project works as a joint team, with the academic and GSK scientists sharing data and working toward common goals. Through this arrangement, academic researchers benefit from GSK’s capabilities in medicinal chemistry and resources, such as state-of-the-art high-throughput screening technology — the expertise and automated equipment required to quickly and accurately screen millions of potential drug compounds for activity against a selected cellular target.

"We are honored to be selected to collaborate with GSK," said David A. Brenner, MD, vice chancellor for health sciences and dean of UC San Diego School of Medicine. "Paired with GSK’s expertise, our collaborative cancer stem cell research infrastructure, bolstered by the California Institute for Regenerative Medicine, National Cancer Institute and philanthropist T. Denny Sanford, places our DPAc team in the best possible position for success."

To be considered for DPAc, academic research proposals must have a clear therapeutic hypothesis, a defined target that can likely be addressed with a drug-like molecule and be led by researchers with deep target and disease expertise, access to model systems and clinical samples to progress the target.

"The GSK DPAc program is highly selective and works to identify the best academics with the best targets for partnership," said Carolyn Buser-Doepner, PhD, vice present and global head of DPAc at GSK. "The UC San Diego collaboration represents several firsts for the DPAc team at GSK — it is our first target in the emerging area of RNA editing and it is our first bench-to-bedside DPAc collaboration with a California university. Furthermore, Dr. Jamieson is an ideal collaborator with deep target and disease expertise, a highly productive preclinical research team with access to clinical samples and the demonstrated ability to translate studies into the clinic."

"Academic researchers do science well, but we often need industry partners to help translate those discoveries into new therapeutics that will make a difference to patient lives," said Ida Deichaite, PhD, director of industry relations at Moores Cancer Center. "This DPAc arrangement is a first for the University of California and will hopefully provide a model for future collaborations."

In addition to a strong collaborative infrastructure, Jamieson credits major support from School of Medicine and Moores Cancer Center leadership, including Brenner, Lawrence Goldstein, PhD, director of the Stem Cell Program, Wolfgang Dillmann, MD, chair of the Department of Medicine, and Scott Lippman, MD, director of the Moores Cancer Center.

"This is a wonderful example of academia-industry collaboration to accelerate drug development and clinical impact," said Lippman, "and opens the door for cancer stem cell targeting from a completely new angle — inhibition of aberrant RNA editing."

"Groundbreaking research on the basic behavior of stem cells — during human development and in the pathology of disease — has long been one of our strengths at UC San Diego," said Goldstein, who is also scientific director of the Sanford Consortium for Regenerative Medicine and director of the Sanford Stem Cell Clinical Center. "Now, those fundamental studies are paying off, as we begin to apply that information in the development of new therapies."

On July 8, 2015 Janssen Diagnostics reported that its CELLSEARCH System technology was used in new research demonstrating the ability to detect PD-L1 expression on circulating tumor cells (CTCs) (Press release, Johnson & Johnson, JUL 8, 2015, View Source [SID:1234506187]). The results of this research appear in the article, "Frequent Expression of PD-L1 on Circulating Breast Cancer Cells," published online in Molecular Oncology, and demonstrate that PD-L1 positive CTCs were found in 11 out of 16 (68.8%) patients with circulating tumor cells.

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This particular application of the CELLSEARCH System is for research purposes only and has not been cleared by the US Food and Drug Administration. This publication potentially adds a new important application to the research use of the CELLSEARCH System to characterize CTCs for PD-L1. In performing their research, the investigators selected the CELLSEARCH System as an automated technical platform that has demonstrated consistent, reproducible results.

The importance of immune checkpoint regulators in oncology is becoming more widely understood and has given rise to the development of immunotherapies for cancer treatment. PD-L1 is an immune checkpoint regulator targeted by a number of approved and developmental oncology therapies. These results indicate that CTC analysis for PD-L1 expression is feasible and when confirmed, could open up the opportunity to predict response to certain therapies in future, larger studies using a blood test rather than tissue biopsy. In a research setting, the CELLSEARCH System offers the ability to capture CTCs via a routine blood test.

"I believe we have demonstrated that CTC characterization for PD-L1 expression is feasible using a CTC platform. This paves the way for the utilization of a CTC/PD-L1 assay in future clinical trials to explore whether it can stratify patients according to response, and potentially predict the efficacy of immune checkpoint blockade," comments study investigator Catherine Alix-Panabières, Ph.D., Director of the Laboratory of Rare Human Circulating Cells, University Medical Centre of Montpellier, University of Montpellier EA2415, Montpellier, France.

CTCs have the potential to allow real-time, dynamic monitoring of tumor characteristics without the need for repeated invasive biopsies. It was demonstrated earlier that CTC expression of key biomarkers such as HER21, IGFR2, c-MET3 and other proteins can be monitored successfully. This publication in Molecular Oncology underscores the potential of CELLSEARCH CTC testing to also become an important tool in cancer immunotherapy.

About CELLSEARCHSystem Technology

The CELLSEARCH System was honored with a Prix Galien USA Award in 2009 for Best Medical Technology on the basis of the innovative nature of its development, applicability and future biomedical potential.

For further information, please refer to the CELLSEARCH CXC Kit Instructions for Use at www.cellsearchruo.com. The application of the CELLSEARCH System described in this study is for research use only, and not for use in diagnostic procedures. The performance characteristics, safety, and effectiveness for this application have not been established and are not cleared or approved by the FDA.