And pushing ahead they are. In just over a year since its establishment with support of a five-year, $102,265,000 pledge from Pelotonia, the PIIO has developed a strategic plan and recruited eight staff members and 10 scientists with expertise ranging from development of cancer vaccines to bioinformatic and statistical modeling for high-throughput immunogenomic screening. These scientists bring the total number of researchers working on immunooncology approaches to clinical trials at the OSUCCC – James to over 60.
Moreover, PIIO members have obtained $16 million in annual funding from new grants (including $13 million from the NIH), published more than 265 peer-reviewed articles, launched some 20 clinical trials, added 10 technologies to the institute’s Immune Monitoring and Discovery Platform (IMDP), and entered research agreements with corporations such as Alphamab Oncology, Heat Biologics, Genentech and others. In addition, the PIIO has initiated a cancer immunotherapy cohort database that will help scientists determine risk factors associated with efficacy and adverse drug events related to cancer immunotherapies.
Li is proud of the first-year accomplishments of the PIIO, a comprehensive bench-to-bedside research initiative focused on harnessing the body’s immune system to fight cancer at all levels — from prevention to treatment and survivorship. “We are passionate, curious and driven in our pursuit of unleashing the potential of immunotherapy in cancer care,” he says. “Today we have a strong framework and enhanced research capabilities that position our team to make big strides in the coming years. Now it is time to do the next phase of fundamental and translational work.”
That work includes plans to open up to 130 immuno-oncology clinical trials over the next five years and to create a pipeline of novel cancer immunotherapeutics, many of them driven by Ohio State discoveries that will be tested at patient bedsides.
The PIIO has already opened clinical trials aimed at making immuno-oncology drugs safer and more effective for patients. It also has initiated a first-in-human trial to evaluate the use of a monoclonal antibody that may sensitize patients toward antitumor immunity. This trial is being tested in patients with locally advanced and metastatic solid tumors at the OSUCCC – James.
“We’re developing superior capabilities in immune-monitoring, artificial intelligence and immuno-informatics to accelerate the development of cancer immunotherapies. This work will ultimately result in treatments that are more effective and less toxic, perhaps even resulting in cures. It’s a very exciting time to be part of this research,” says Li, who expects to recruit an additional 20 researchers to the PIIO over the next two years.
Scientists recruited to Ohio State and as members of the PIIO in the past year include:
- Yiping Yang, MD, PhD, professor and director of the Division of Hematology;
- Bei Liu, MD, MPH, professor in the Division of Hematology;
- Ephraim Ansa-Addo, PhD, assistant professor in the Division of Medical Oncology;
- Feng Hong, MD, assistant professor in the Division of Medical Oncology;
- Chan-Wang “Jerry” Lio, PhD, assistant professor in the Department of Microbial Infection and Immunity;
- Xingjun Wu, PhD, research assistant professor in the Division of Medical Oncology;
- Gang Xin, PhD, assistant professor in the Department of Microbial Infection and Immunity;
- Dongjun Chung, PhD, associate professor in the Department of Biomedical Informatics; and
- Margaret Gatti-Mays, MD, MPH, FACP, assistant professor in the Division of Medical Oncology.
To guide the research efforts of PIIO scientists, the institute has organized into four interconnected centers of research excellence:
- Cancer Immuno-Genomics, 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, where 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 (NK) 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, 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 of research excellence are:
- Immuno-Informatics (Data Science), where 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.
Recent PIIO research highlights include:
- A study led by the laboratory of Thomas Mace, PhD, of the Translational Therapeutics Program at the OSUCCC – James, that revealed a mechanism for CD200 gene expression in the pancreatic tumor microenvironment (TME) to promote immunosuppression. This study discovered elevated expression levels of CD200 in the pancreatic TME and increased expression of the receptor (CD200R) by myeloid-derived suppressor cells (MDSC) in patients. Antibody blockade of CD200 in preclinical animal models of pancreatic cancer was found to limit tumor growth, reduce intra-tumoral MDSC and enhance checkpoint blockade immunotherapy. The findings were reported in the Journal for the Immunotherapy of Cancer (JITC).
- The Ohio State University Corporate Engagement Office granted Zhiwei Hu, PhD, MD, and his team an Accelerator Award for their project titled “Targeting Pathological Neovasculature for Treatment of Advanced Triple-Negative Breast Cancer (TNBC) Using Tissue Factor-Recognizing Chimeric Antigen Receptor (CAR)-Engineered Natural Killer and T Cells.” This technology, specific to a new target in TNBC, may prevent recurrences and have fewer side effects than current treatments.
- Ephraim Ansa-Addo, PhD, and his collaborators published in the journal Science Advances an article titled “RNA Binding Protein PCBP1 is an Intracellular Immune Checkpoint for Shaping T-Cell Responses in Cancer Immunity.” This study demonstrated a critical role for the PCBP1 protein as an intracellular immune checkpoint for maintaining Teff cell functions in cancer immunity. Ansa-Addo’s lab seeks to define how cellular and molecular regulators determine the functions of Tregs in the tumor microenvironment and to use these insights to leverage current treatment approaches in cancer immunotherapy.
- The PIIO also is assisting in immunotherapeutic studies relating to the COVID-19 pandemic. Li’s lab, for example, is participating in a multi-center onco-immune phase III clinical trial of CD24Fc to treat patients hospitalized with COVID-19. The novel coronavirus SARS-CoV-2, which causes COVID-19, promotes inflammation that worsens clinical symptoms. CD24Fc is a first-in-class biologic that fortifies an innate immune checkpoint against excessive inflammation caused by tissue injuries. This study is assessing CD24Fc safety and efficacy in patients exhibiting severe clinical symptoms.
Pointing out that the PIIO is a vast team effort, Li expresses gratitude to all who have contributed.
“We thank OSUCCC – James leaders, our external and internal scientific advisory boards, our strategic planning committee, and the faculty and staff who make up the PIIO for all of their hard work,” he says. “Most importantly, we thank the Pelotonia community — the riders, virtual riders, volunteers, donors and cancer survivors who are raising funds for cancer research. By working together to advance the promising discipline of immuno-oncology, we are pursuing our shared vision of a cancer-free world.”