Investing in the future of cell therapy and immuno-oncology

Inside a small bag that attaches to a tube in a patient’s arm is the future of cancer treatment. Within a bag of thick liquid are cells that have been harvested from the patient’s own blood, then re-engineered in a lab to become a personalized army of highly effective, microscopic serial killers with one mission: Target and destroy cancer cells on sight.

It sounds like something out of a science fiction movie, but it represents the way cancer scientists are harnessing the power of cellular and immune-based cancer therapies at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and the Pelotonia Institute for Immuno-Oncology (PIIO).

In a conversation with Modern Healthcare Custom Media, Dr. Zihai Li, founding director of the PIIO, and Dr. Yiping Yang, director of the Division of Hematology at The Ohio State University College of Medicine, discuss how they are advancing the field of immuno-oncology for the benefit of patients impacted by cancer.

Dr. Zihai Li is a career immunologist and a board-certified medical oncologist. In 2019, he became the founding director of the Pelotonia Institute for Immuno-Oncology at the OSUCCC – James, where he guides this benchto- bedside initiative that is a leader in driving immunooncology breakthroughs toward cancer cures.

Dr. Yiping Yang is a nationally recognized expert in cancer immunology and immunotherapy who serves as the director of the Division of Hematology at the OSUCCC – James. His research interests focus on tumor immunology and viral immunity, with the ultimate goal of developing effective immunotherapy approaches for treating cancer. Dr. Yang is also a member of the Leukemia Research Program at the OSUCCC – James.

Dr. Yiping Yang: Immuno-oncology is a field of study that develops cancer therapeutics that target the immune system. This is an exciting clinical program that is now broadly used in many types of cancers, and some immuno-oncology therapeutics are first-line therapy.

YY: Immuno-oncology is not a new idea but is considered a new treatment modality for clinical application in addition to surgery, radiation therapy, and medical therapies such as chemotherapy and genomic-targeted drug therapies.

YY: The most promising advancement to date is the development of immune checkpoint blockers such as those targeting PD1, PDL1 and CTLA4 molecular pathways, which have been found effective for more than 20 forms of cancer. These have brought highly effective drug options to diseases with limited effective treatment options, such as melanoma and lung cancer. In the past five years, cell therapy-based treatments, particularly CAR T-cell (chimeric antigen receptor T cells) therapy, have also shown considerable promise. The OSUCCC – James was among the first hospitals in the United States to begin administering CAR T-cell therapy for lymphoma, and has since treated about 360 patients with this highly sophisticated therapy. Our clinical and translational expertise in this field make us one of the most experienced teams in the United States studying and delivering CAR-T. Earlier this year, Dr. Marcos de Lima joined the OSUCCC – James to lead its Blood and Marrow Transplant and Cellular Therapy programs, which work hand-in-hand to conduct research and treat patients with cancers of the blood, also known as “liquid” tumors. It’s a very exciting time to be working in immuno-oncology, and at the OSUCCC – James in particular. In less than two years, we have established a robust infrastructure to conduct immunooncology research at Ohio State, and we are poised to be a hub of innovation for cancer immunotherapies that will help patients in Ohio and beyond.

Dr. Zihai Li: The development of immuno-oncology combination therapies—such as immune checkpoint blockers with cell therapy or with other targeted therapy—will likely revolutionize this field. Immunotherapies targeting other mechanisms provide many new and exciting options for patients, and targetable pathways are discovered all the time.

ZL: It is critical to continue investing in immuno-oncology research programs because this field offers very promising therapeutic advancements that will change the landscape of cancer care. The immunotherapeutic approach offers greater precision and specificity with fewer side effects. Despite the extraordinary work done by scientists around the world for decades and the substantial improvement in cancer care, we are not “home free”—current immunotherapies work in only about 20% of all patients, and many patients develop resistance. This is not good enough. We must continue to develop new and better agents and translate these discoveries into the clinic to ensure that clinicians have a broad arsenal of optimal treatment options.

ZL: The PIIO is unique in its ability to bring together investigators from a wide range of specialties. We emphasize team science and utilize the broad expertise on our team to implement cutting-edge technologies to understand the immune system and make discoveries. A key initiative of the PIIO is to ensure that our research is focused on translation, which is facilitated by being located at a National Cancer Institute-designated comprehensive cancer center aligned with an affiliated academic medical center on the campus of one of the nation's largest public universities. Using these resources, including access to a broad patient population, a wide range of clinical trials, electronic medical record interfacing for artificial intelligence and big data, we focus on understanding the immune system in the context of cancer, developing good models and translating our discoveries from the bench to the bedside.

ZL: The ultimate goal of the PIIO is to cure cancer using immunotherapy. However, we also focus on improving survival and cancer prevention, for example, through research aimed at developing cancer vaccines.

ZL: The answer to this question requires many voices and perspectives. We need new thinking for health care delivery, as many of our current models cannot meet the needs of immuno-oncology therapeutic development. For instance, the development of cell therapies is exceptionally expensive from both a research-and-development and a clinical-application standpoint. Our biggest challenge is a lack of infrastructure to develop and use these therapies in a cost-effective manner. This is not unique to Ohio State or academia—the government and the pharmaceutical industry also struggle with how to support an immuno-oncology pipeline in an affordable way.

The new National Institutes of Health Advanced Research Projects Agency for Health (ARPA-H) reflects the broad understanding of this issue among agencies. ARPA-H is trying to solve some of the problems around discovery translation. For example, quick, cost-effective translation, and the use of new technologies for diagnosis. Our hope is that academic institutions can continue to expand translational capacity through collaborations with pharma, adding pharmaceutical production facilities, bringing in venture capital to support promising drug development, and engaging in other collaborations that advance overall immuno-oncology discovery.

ZL: Founded in 2019, the PIIO provides a collaborative environment for over 100 scientists from across Ohio State who work in immuno-oncology. We expect to recruit an additional 20 researchers to the PIIO over the next three years, including both established senior faculty and junior researchers.

A key pillar of our work includes ambitious plans to open up to 130 immuno-oncology clinical trials over the next five years and create a strong pipeline of new cancer therapeutics driven by Ohio State discoveries that will be developed for clinical application.

Clinician scientists within the PIIO have already opened several clinical trials aimed at making immuno-oncology drugs safer and more effective for patients. For example, we initiated a first-in-human trial to evaluate the therapeutic impact of a monoclonal antibody that may sensitize patients toward antitumor immunity.

To guide PIIO research efforts, we have organized the institute into four interconnected centers of research excellence:

• Cancer Immuno-Genomics is a program conducted in partnership with Nationwide Children’s Hospital that involves understanding the relationship between cancer genomics and immune evasion and includes epigenetics, neo-antigen vaccine, epitope prediction, TCR repertoire analysis, HLA typing and CRISPR screening;
• Cell therapy in which immune cells are collected from a patient’s blood, engineered and returned to that patient to target and eradicate cancer. This includes adoptive cell therapy with T cells and natural killer cells;
• Systems immuno-oncology, which seeks a better understanding of cellular systems to create more efficient and effective immunological tools to fight cancer and includes immune regulation, microbiome, NK and T cell biology, and tumor microenvironment;
• Translational immuno-oncology is an area that focuses on transforming immuno-oncology discoveries into new or improved cancer treatments applicable at patient bedsides. This team works with the Drug Development Institute at the OSUCCC – James on developing new drug therapies.

Integral to each center are:

• Immuno-informatics, in which big data and quantitative science are used to improve immuno-oncology research; this includes machine learning, neo-antigen discovery, spatial statistics, etc.
• Immune monitoring and discovery, which is backed by a new facility with technology that allows scientists to get a 360-degree view—down to the single-cell level—of what happens in the immune system during treatment with immuno-oncology agents.