UPDATED: December 16, 2020
Even before the World Health Organization (WHO) declared a global pandemic in January 2020, experts were discussing cases of severe immune reactions to SARS-CoV-2, the virus that causes COVID-19, and debating how to address it while racing to create a new vaccine. The Cancer Research Institute (CRI) is fortunate to have many of the world’s leading researchers in immunology and cancer immunotherapy on its Scientific Advisory Council, many of whom are offering their knowledge, experience, and insight to help during the current crisis.
Illuminating Immune System Response
The laboratory of CRI Scientific Advisory Council Associate Director E. John Wherry, Ph.D., at the University of Pennsylvania has used a variety of approaches in immunology to offer key information. His lab is focusing on how peripheral changes in the immune response can inform clinicians of the best strategies to treat patients. An analysis of 1,293 pregnant women in Philadelphia, published in Science Immunology, found the rate of virus exposure among Black and Hispanic women to be five times higher than among White and Asian women. An analysis of 125 COVID-19 patients, published in Science, identified three “immunotypes” associated with poor clinical trajectories versus improving health. An analysis of Multisystem Inflammatory Syndrome in Children (MIS-C), a condition associated with pediatric cases of COVID-19, is forthcoming.
The immune status of a COVID-19 patient may be a strong determinant of the appropriate treatment at the right time—immunosuppressants may be effective for some but detrimental for others. CRI Scientific Advisory Council Associate Director Jedd Wolchok, M.D., Ph.D., suggests the use of immunotherapies in cases where the immune system has become “exhausted” and needs reinforcements. With his colleague Santosha A. Vardhana at Memorial Sloan Kettering Cancer Center (MSKCC), he explored the characteristics of COVID-19-induced cytokine storms and immune dysregulation and published their findings the Journal of Experimental Medicine. In addition to Wolchok, other MSKCC clinicians have also been investigating immune responses against COVID-19, including Clinical Accelerator Clinical and Scientific Advisory Committee member Marcel van den Brink, M.D., Ph.D., who is leading a clinical trial testing a treatment that targets the interleukin-7 (IL-7) pathway.
A team of researchers, including CRI Scientific Advisory Council member Nir Hacohen, Ph.D., examined the relationship between SARS-CoV-2 lung infection and patients' immune response (Nature Communications).
Offering Approaches to Treatment
Early on, doctors recognized the presence of overactive immune responses—known as cytokine storms—in the lungs and other organs in some patients with severe cases of COVID-19. CRI physician-scientists pioneering immunotherapy in cancer patients were among the first to encounter this severe immune-related side effect, and have provided the foundation for better understanding this phenomenon in the context of this coronavirus.
CRI Scientific Advisory Council member Carl June, M.D., at the Perelman School of Medicine at the University of Pennsylvania, has long dealt with cytokine storms arising from CAR T cell therapy and used an immunosuppressive antibody—known as tocilizumab—to combat this potentially life-threatening side effect—and approach doctors are also using in COVID-19. Dr. June, who was infected with the coronavirus and has recovered, co-authored an article in Science with lessons for treating cytokine release syndrome in severe COVID-19 patients. He has also developed, in collaboration with David Fajgenbaum, M.D., MBA, MSc, FCPP, a unifying definition of cytokine storm to help physicians assess and treat patients with this form of immune dysregulation (New England Journal of Medicine).
Karen Weintraub of USA Today spoke with Dr. June about tocilizumab, which he used to treat Emily Whitehead and is currently being used in COVID-19, and Dr. Wherry about the importance matching the right drugs with the right patients.
CRI Scientific Advisory Council member Cassian Yee, M.D., of the University of Texas MD Anderson Cancer Center, along with Drs. Kevin McHugh and Peter Lillehoj of Rice University, is designing a point-of-care device for the rapid identification of COVID-19 patients who are likely to require the most medical assistance. They plan to automate the process of immune cell quantification with an inexpensive microfluidic device.
Accelerating Vaccine Development
CRI Scientific Advisory Council member Nina Bhardwaj, M.D., Ph.D., of the Icahn School of Medicine at Mt. Sinai, has been awarded a grant for “Deconvolution of SARS-Cov-2-specific immune responses in COVID-19 patients for broadly effective vaccines” by the Pershing Square Foundation.
A team of researchers at the University of Pennsylvania helped create the mRNA technology used in two COVID-19 vaccines. Dr. E. John Wherry deployed this same technology in studying the immune response of hospitalized COVID-19 patients, which helped inform vaccine design.
CRI Scientific Advisory Council member Susan M. Kaech, Ph.D., discussed the mRNA-based COVID-19 vaccine developed by Pfizer and BioNTech with KUSI News.
Understanding Cancer and COVID-19
Dr. Wherry discussed COVID-19 vaccine development at the AACR Virtual Meeting: COVID-19 and Cancer (July 20-22), where several CRI Scientific Advisory Council members presented. Elizabeth Jaffee, M.D., of the Johns Hopkins University School of Medicine, discussed the effects of cancer immunotherapies on patients with COVID-19, both those with and without cancer, whereas Charles Drake, M.D., Ph.D., of Columbia University Medical Center, discussed repurposing cancer drugs to treat COVID-19, notably blocking interleukin-8 (IL-8) to treat hospitalized patients.
Dr. Drake also discussed immunotherapy clinical trials during COVID-19 with the ASCO Post, including donning additional protective equipment, deciding which trials should stay open, and incorporating telemedicine.
Whether cancer immunotherapy increases or decreases risk of severe COVID-19 is still unclear and studies are ongoing. One retrospective study at Memorial Sloan Kettering Cancer Center, to which Dr. Wolchok contributed, suggested cancer patients receiving immunotherapy were at increased risk for severe outcomes from COVID-19. However, in a paper for Clinical Cancer Research, Dr. Wolchok argued that investigation into the use of immune checkpoint inhibitors in cancer during COVID-19 was required and that the timing was key.
In addition to tracking the impact of COVID-19 on oncology clinical trials, the CRI Anna-Maria Kellen Clinical Accelerator has launched a new clinical trial investigating recombinant human interleukin-7 (CYT107)—a cytokine that has been used to increase the levels of T cells in a variety of other diseases. This study could lead to important insights both for treating both COVID-19 and cancer. Dr. van den Brink leads the trial at Memorial Sloan Kettering Cancer Center, and Joseph Nates, M.D., at MD Anderson Cancer Center.
On June 18, the Cancer Research Institute hosted a live stream event during which Dr. June, Dr. Wherry, and Miriam Merad, M.D., Ph.D., of the Icahn School of Medicine at Mount Sinai, discussed many of these emerging developments. The event was moderated by Matthew Herper of STAT.
Ultimately, the experts felt that the pandemic has sharpened society’s appreciation for science, as the insights gained from cancer immunotherapy and fundamentals of immunology will be necessary to end this public health crisis.
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