After living through the COVID-19 pandemic over the past year, it’s understandable that most people consider viruses to be our enemies causing illness and harm to humans. However, this outlook fails to consider the many surprising advantages these submicroscopic collections of genetic code afford scientists in pushing the boundaries of medicine.
Viruses have honed advantageous skills over billions of years of evolution to invade and hijack the cellular machinery of living organisms, including bacteria, fungi, animals and, importantly, humans. As such, this ability to manipulate life has enabled researchers to gain insights into how best to exploit this advantage for good. This effort has already yielded new biological therapies to treat a wide range of diseases, including rare, inherited disorders treated with gene and cellular therapies, antimicrobial-resistant infections treated with bacteriophages, and even cancer through oncolytic viral treatments. In recent years, the biotechnology and pharmaceutical industry has invested many resources to convert viruses to be beneficial to human health and serve as valuable allies in the fight against other harmful illnesses.
One such ally-in-training is the Epstein-Barr virus (EBV). Despite being known to many as the cause of infectious mononucleosis (mono), most people are infected by EBV at some point in their lives without even knowing it, as these infections are often kept in check by the immune system. In fact, more than 90% of adults are infected with EBV, which establishes lifelong memory immune cells which wait to come back to fight the EBV virus when needed. Due to its latency, EBV has been associated with several forms of cancer and autoimmune diseases in which a patient’s immune system is no longer able to adequately fight the virus. These associated conditions include Hodgkin’s lymphoma, Burkitt’s lymphoma, gastric cancer, nasopharyngeal carcinoma, conditions associated with HIV such as hairy cell leukemia, and even multiple sclerosis (MS). Multiple studies have established an important link between EBV infection and MS pathogenesis, with some specifically showing B cells positive for EBV reside within the brain lesions of MS patients.
However, after decades of research into the biology and pathogenesis of EBV, several key characteristics of the infection have been identified. By focusing on its potential to combat disease, scientists have transformed the former disease-causing agent to become the basis of technology for new therapeutic approaches. This is feasible due to an inherent ability to traffic to the root cause of certain diseases and the lifelong persistence of EBV in an individual. For patients with EBV-infected cells causing illness, allogeneic EBV T cells from donors are being investigated to replenish and enhance a patient’s natural immune function and directly target the underlying cause of EBV-associated cancers or autoimmune diseases. Additional attributes of EBV T cells include a low likelihood to harm normal tissues, which may enhance tolerability and the ability to persist in the body long enough to fight the disease, offering the potential for durable response.
Researchers have begun uncovering the potential of this technology to more precisely target and treat EBV-driven diseases. This includes immunotherapies currently in development to treat EBV+ PTLD (Epstein-Barr virus associated post-transplant lymphoproliferative disease) and MS. People infected with EBV, representing most adults, have a supply of immune cells already programmed to specifically fight EBV (EBV-targeted T cells). These EBV T cells are present in large quantities in the blood allowing these cells to be easily donated by healthy individuals and transferred to benefit patients with an EBV-associated disease. This type of allogeneic or “off-the-shelf” immunotherapy offers many other benefits that may overcome several key issues in cell therapies, including the risk of immunogenicity and the immediate availability of high-quality cell therapy products. In fact, since healthy EBV T cells can be donated, manufactured, stored and made readily available when required by another individual, allogeneic EBV T cells have the potential to transform the treatment of diseases associated with EBV.
Additionally, researchers are investigating next-generation cell therapies designed to retain the potential benefits of EBV T cells to attack targets on blood cancers and solid tumors. By modifying T cells to express a specific receptor called chimeric antigen receptors (CARs) against a cancer-specific antigen target, these CAR T-cell treatments may be able to target solid tumors. This hurdle has yet to be overcome. Should this be the case, allogeneic CAR-Ts may significantly expand the number of patients amenable to this type of treatment, offering hope to those with cancer or loved ones with the disease.
Despite the common mistrust of these infectious agents, viruses are increasingly becoming allies in the fight against other harmful diseases. By leveraging certain properties of viruses that are beneficial to human health, clinicians can now offer treatments for life-threatening conditions that previously had no therapeutic options. As we continue to explore and research how viruses impact human health, scientists will inevitably find new ways to exploit viruses and protect humans from disease.
Cokey Nguyen is senior vice president and chief scientific officer of Atara Biotherapeutics, where he is focused on leading the development of next-generation allogeneic cell therapies for cancer and autoimmune diseases. With his passion for delivering transformative therapies to patients, Nguyen is eager to both advance Atara’s existing programs and further expand the pipeline through pioneering science, teamwork and a commitment to excellence.
Prior to joining Atara, Nguyen was at Fate Therapeutics, where, as Vice President, Innovation, Research and Development, he directed strategy for discovery and innovation efforts, and spearheaded the corporate collaboration program with ONO Pharma. Prior to that, he was leader of the targeted immunotherapy group on the Oncology R&D team at Pfizer, producing bispecific antibodies for solid tumors and hematological malignancies and bringing them into the clinic.
Nguyen received his undergraduate degree in biology from Harvard College and a Ph.D. in immunology from Washington University in St. Louis. He was a postdoctoral associate at the Center for Cancer Research at the Massachusetts Institute of Technology (MIT), where he focused on the identification and characterization of BRCT domains as novel phospho-binding domains in DNA damage pathways.
Filed Under: Drug Discovery, Immunology