The Cancer Research Institute (CRI)’s focus on immunology research—while primarily aimed at curing cancer—also has contributed to advances in the treatment and prevention of infectious diseases including HIV/AIDS, hepatitis C, HPV, and influenza, and has direct bearing on efforts to treat and prevent infection with SARS-CoV-2, the virus that causes coronavirus disease (COVID-19).
CRI physician-scientists pioneering immunotherapy in cancer patients, including Carl June, M.D., at the Perelman School of Medicine at the University of Pennsylvania, were among the first to encounter a severe immune-related side effect called “cytokine storm” within the context of treating patients with a powerful new type of T cell therapy. Their experience in overcoming this storm by giving an immunosuppressive antibody is helping doctors combat the same syndrome seen spontaneously in patients with COVID-19, whose immune systems can respond violently to infection with the virus and inadvertently attack their lungs in the process. Dr. June, who was infected and has recovered, recently co-authored an article in Science with lessons from arthritis and cell therapy in cancer patients for treating cytokine release syndrome in severe COVID-19.
Two CRI CLIP Investigators—Hilary Ann Coller, Ph.D., of the University of California, Los Angeles, and Vinodh Pillai, M.D., Ph.D., of the Children’s Hospital of Philadelphia—are extending their current CRI-funded research projects into the study of cytokine storm. Dr. Coller is investigating how autophagy (a cellular degradation pathway) in the stroma might influence the response to immunotherapy. Her team believes to have found an important model for understanding the role of genetic predisposition in the response to cytokine storm-inducing effects and plans to test the effects of age and hydroxychloroquine in this model. Dr. Pillai is studying levels of CD19 in CAR T cell therapy for children with B cell leukemia.
CRI Technology Impact Award recipient Muneesh Tewari, M.D., Ph.D., of the University of Michigan in Ann Arbor is also adapting his CAR T cell therapy work to help with COVID-19. His CRI-funded research project to measure cytokines in CAR T cell therapy patients is still in development, but his collaborator Dr. Kurabayashi is looking to use the platform in critically ill COVID-19 patients. Additionally, a wearable sensors study (temperature, heart rate) originally for CAR T cell therapy patients is shifting to evaluating health care providers given their potential risk of exposure to the virus. His team is also applying expertise in digital polymerase chain reaction (PCR) to COVID-related questions, using residual biospecimens from the clinical lab at the university.
CRI-funded research originally intended to help cancer patients respond to immunotherapy is now helping accelerate development of COVID-19 treatments. For example, a gene technology developed with CRI funding by Brian Brown, Ph.D., at the Icahn School of Medicine at Mount Sinai to identify new therapeutic targets in cancer patients is now being used to map genetic drivers of immune responses in SARS-CoV-2-infected patients.
Another CRI scientist, Katie Campbell, Ph.D., at the University of California, Los Angeles, is helping accelerate vaccine development against COVID-19 by recently publishing a database of potential SARS-CoV-2 targets that she has predicted through computational analysis are most likely to be effective targets against the virus based on their likelihood of being “seen” by the immune system as dangerous.
CRI Fellow Ido Yofe, Ph.D., of the Weizmann Institute of Science in Rehovot, Israel, normally uses genomics technology to profile each cell within tumors individually, in order to dissect the most subtle features and immune cell interactions found in each patient’s tumor, and understand how immunotherapy treatment alters them. Today, he is part of a team working to establish a new method of gene sequencing for testing mass volumes of people for COVID-19.
Several CRI scientists are using their laboratory knowledge and experience to assist in research and testing. CRI Fellow Michael J. Hogan, Ph.D., of the Children’s Hospital of Philadelphia is collaborating with colleagues at the University of Pennsylvania to evaluate the T cell response in mice immunized with a COVID-19 mRNA vaccine encoding the SARS-CoV-2 spike protein. He was well positioned to pivot to this crucial work given his CRI-funded research project. Dr. Hogan has been studying the cellular pathways of helper T cells in response to influenza virus in mice. Because helper T cells recognize viral infections and cancer in the same manner, these results should be directly applicable to the development of more effective vaccines and immunotherapies for cancer as well as infectious diseases like COVID-19.
CRI Fellow Duncan Robert McKenzie, Ph.D., of the Francis Crick Institute in London has begun contributing to a high-throughput immunomonitoring study of COVID-19 patients at King’s College London (KCL), a team project developed by his sponsor, Adrian C. Hayday, Ph.D., FMedSci, and funded through KCL. Dr. McKenzie will be using his experience with virus handling, cell preparation, and flow cytometry to assist this large-scale effort. (He is also preparing a manuscript on his CRI-funded project on epidermal intraepithelial lymphocytes and the molecular processes of cancer immunosurveillance.)
Some CRI scientist-clinicians have been deployed to treat COVID-19 patients. CRI grantee Gavin Peter Dunn, M.D., Ph.D., of Washington University School of Medicine in St. Louis, MO, who normally studies brain tumors and cancer vaccines, has been called up by the Naval Reserve as a medical professional to help with the COVID-19 pandemic. CRI Technology Impact Award recipient Adam Mor, M.D., Ph.D., of Columbia University Medical Center in New York City has been re-assigned to care for COVID-19 patients in the hospital. Dr. Mor still draws connections to his research (currently on hold), noting that T cell exhaustion in the context of cancer is very similar to viral diseases.
CRI scientists have also volunteered their expertise and their labs in the current crisis. CRI Lloyd J. Old STAR Yvonne Chen, Ph.D., of the University of California, Los Angeles, has volunteered her lab’s service to the UCLA hospital system if there is anything, such as PCR-based testing, with which they can assist. CRI Fellow Miguel Reina-Campos, Ph.D., of the University of California, San Diego, has volunteered for the San Diego COVID Research Enterprise Network (SCREEN), which is supporting the Microsetta Initiative in collecting and preserving SARS-CoV-2 viral RNA to help researchers better understand how the virus spreads. CRI Fellow Li Zhang, Ph.D., of Weill Cornell Medicine in New York City joined the Crowdfight COVID-19 community to contribute her expertise to researchers in need.
Cancer patients and other immunocompromised individuals are among those at greatest risk of contracting COVID-19. CRI’s research to develop cancer treatments that do not weaken patients’ immune systems but instead empower them will help over time to reduce the number of people who are more vulnerable to infectious diseases like COVID-19.
CRI is currently surveying its international community of immunologists and tumor immunologists to learn how they are lending their expertise to combatting the COVID-19 pandemic. We look forward to sharing more stories of CRI impact in both this acute health crisis and the longer-term fight against cancer.
UPDATED: April 22, 2020
Photo by Patrick Assalé on Unsplash