Every year, 14 million people around the world, including 1.7 million Americans, are diagnosed with cancer. One of the major challenges in fighting cancer is to understand and manipulate the response of the body's immune system to cancer cells. Recently, an area that has received growing attention and has shown promise in clinical trials is the use of immune checkpoint inhibitors.
On the University of Colorado Anschutz Medical Campus, Drs. Richard Schulick and Yuwen Zhu have identified a series of novel checkpoint inhibitors and are now partnering with GSK (GlaxoSmithKline), a leading pharmaceutical company, to push their discoveries forward, with the aim of bringing new medicines to patients worldwide.
Our immune system is programmed to attack foreign cells, viruses, and microbes to protect us from illnesses. But how does it differentiate what is foreign and what is “self”? The answer is a two-way signaling mechanism.
The first type of signaling triggers an immune response when abnormal cells are detected. As cancer cells grow and multiply, they mutate their DNA unceasingly, which causes them to produce proteins that are different from those of normal cells. Due to small changes in their peptide sequences, cancer cells express defective neo-peptides (or neo-antigens) which can be detected by the immune system, triggering T cells (the “soldiers of the body”) to destroy the cancer cells.
The second type of signaling acts in the opposite direction, decreasing or turning off the immune response via a “checkpoint” mechanism. This kind of signaling evolved to prevent the body from inadvertently attacking its own healthy cells. Unfortunately, as cancer cells mutate, they sometimes manage to activate the checkpoint mechanism, turning off the body’s immune response. Therefore, blocking the checkpoint mechanism could be an effective way to reactivate the body’s immune response against cancer cells.
“Cancer has a way of evading the immune system, and when this checkpoint is blocked by an antibody, for example, it can activate the immune system to attack cancer cells,” explained Dr. Richard Schulick, Chair of Surgery at the University of Colorado Anschutz Medical Campus.
“Cancer has a way of evading the immune system, and when this checkpoint is blocked by an antibody, for example, it can activate the immune system to attack cancer cells,” explained Dr. Richard Schulick, Chair of Surgery at the University of Colorado Anschutz Medical Campus.
The novel checkpoint inhibitors developed at the Anschutz Campus were discovered in the lab of Dr. Yuwen Zhu in collaboration with Dr. Schulick. Dr. Zhu published their findings in the Journal of Experimental Medicine. “Basically, we identify new immunomodulatory pathways,” said Dr. Zhu. “In this case, we identified a new immune checkpoint, which has the potential of being targeted to promote anticancer response in cancer patients.”
According to Dr. Zhu, the next steps in the research will focus on cancers that heavily express a particular ligand/receptor pathway, as well cancers that are resistant to existing immunotherapies. “It will provide doctors a new therapeutic option, especially for patients who can’t benefit from existing therapies,” Zhu said. He believes the discovery has broad applications and is not limited to one type of cancer but applies to multiple kinds, with the potential to improve the efficacy of current therapies via a combinatory approach.
CU Innovations, the office responsible for overseeing technology transfer at the Anschutz Medical Campus, saw the potential and worked to find a pharmaceutical partner to bring this revolutionary new science to patients. GSK’s Discovery Partnership with Academia (DPAc) was identified as an excellent fit for developing collaborative research. “GlaxoSmithKline brings world-class pharmaceutical expertise onboard,” said Brian Bellesheim, Business Development Manager at CU Innovations. “They have the right mix of resources and scientific focus to develop new cancer treatments, and the right approach to working with academia, with a commitment to finding cures for disease, in a collaborative fashion.”
CU Anschutz Chancellor Don Elliman expressed his support for innovation and academia-industry collaboration and said he is looking forward to deepening the university’s ties with industry to translate academic discoveries into services and products that will improve and transform healthcare. “Entering into this research collaboration with GSK is a testament to the groundbreaking science taking place at CU Anschutz Campus,” said Elliman.
“Entering into this research collaboration with GSK is a testament to the groundbreaking science taking place at CU Anschutz Campus,” said Elliman.
“We are extremely happy to have faculty members like Drs. Schulick and Zhu who are working to find a cure for one of the biggest challenges of humankind and whose cutting-edge science is opening the doors for broader academia-industry collaboration. We are confident that bringing our world-class researchers and premier pharmaceutical companies like GSK together will lead to a positive impact.”
About Dr. Schulick and Dr. Zhu
Dr. Richard Schulick is the Aragón/Gonzalez-Gíustí Chair of Surgery and specializes in Surgical Oncology. He has completed fellowships in clinical pharmacology and immunology and holds an MBA. In 2015, he was named by Castle and Connolly in the listing of America’s Top Doctors for Cancer. Denver’s 5280 Magazine also named him among Top Doctors in 2015, a listing based on a survey of physicians asking whom they would trust to treat themselves and their families.
Dr. Schulick has authored and co-authored numerous papers on cancer-promoting mechanisms, including “Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline,” “Evolving Trends Towards Minimally Invasive Surgery for Solid-Pseudopapillary Neoplasms,” “Intercellular Adhesion Molecule-1 Mediates Murine Colon Adenocarcinoma Invasion,” “Longer Course of Induction Chemotherapy Followed by Chemoradiation Favors Better Survival Outcomes for Patients With Locally Advanced Pancreatic Cancer,” and “Factors influencing survival in patients undergoing palliative bypass for pancreatic adenocarcinoma.”
Dr. Yuwen Zhu holds a Master of Science in Molecular Biology and a PhD in Immunology. He completed his postdoctoral training at Johns Hopkins University and Yale University, under the direction of Dr. Lieping Chen, one of the pioneers of anti-PD-1/PDL-1 therapy. Dr. Zhu’s laboratory focuses on novel immunomodulatory pathways and their potential application in cancer immunotherapy.
Dr. Zhu has authored or co-authored numerous papers related to his lengthy research on methods to fight cancer. He and Dr. Schulick, together with Dr. Robert Torphy, recently co-authored a paper on Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy. Dr. Zhu’s research has identified several cell surface signaling pathways with therapeutic potentials, including CD28/B7-H2, CD28H/B7-H5, HVEM/SALM5, and CD112R/CD112.
About University of Colorado | Anschutz Medical Campus
The University of Colorado | Anschutz Medical Campus is a premier academic medical center and home to nearly five thousand faculty and three leading healthcare systems, conducting nearly half a billion dollars a year in biomedical research, all for public benefit. The Division of Surgical Oncology is housed in the CU School of Medicine, Department of Surgery. CU Innovations directs technology commercialization at the University of Colorado | Anschutz Medical Campus and on behalf of its hospital affiliates, UCHealth and Children’s Hospital Colorado.
About GlaxoSmithKline, Discovery Partnerships with Academia
Discovery Partnerships with Academia (DPAc) is an innovative approach to drug discovery. As a unit within GSK’s research and development organization, DPAc is dedicated to creating highly collaborative relationships with leading academic researchers. The belief is that working closely together and combining different strengths is a great way to develop new medicines that truly benefit patients.
