Turning CAR-Ts On Infectious Disease

Scientists in Singapore are exploring using immunotherapy traditionally used for cancer on infectious diseases including COVID-19.

AsianScientist (Apr. 24, 2020) – Researchers at Duke-NUS Medical School (Duke-NUS), Singapore, are exploring how engineered T-cells, which have proven successful at treating a range of cancers, could also be applied to tackling infectious diseases. Their findings have been published in Journal of Experimental Medicine.

T-cells that have been genetically engineered to express certain receptors are being used to turn the body’s immune system on cancers. Specifically, chimeric antigen receptor (CAR) or T-cell receptor (TCR) T-cells have revolutionized the way certain cancers are treated, providing a lifeline to previously untreatable patients.

CAR or TCR T-cell therapy involves extracting immune cells, called T lymphocytes, from a patient’s blood and engineering them to express high levels of CAR or TCR. TCRs are naturally found on the surfaces of T lymphocytes while CARs are artificial T-cell receptors that are generated in the laboratory. These receptors allow the engineered T lymphocytes to recognize cancerous or virus-infected cells.

“This therapy is classically used in cancer treatment, where the lymphocytes of the patients are redirected to find and kill the cancer cells. However, its potential against infectious diseases and specific viruses has not been explored,” said Dr. Anthony Tanoto Tan, senior research fellow at the Duke-NUS’ Emerging Infectious Diseases (EID) program and the lead author of the commentary.

“We argue that some infections, such as human immunodeficiency virus (HIV) and hepatitis B virus (HBV), can be a perfect target for this therapy, especially if lymphocytes are engineered using an approach that keeps them active for a limited amount of time to minimise potential side effects.”

This type of immunotherapy requires specialized personnel and equipment, and it needs to be administered indefinitely. This makes it cost-prohibitive for treating most types of viral infections. However, it could be useful for treating certain chronic infections, such as HBV infection where anti-viral treatments merely suppress viral replication.

Treating these patients with a combination of anti-virals and CAR/TCR T-cells could be a viable option. The team’s approach of using mRNA electroporation to engineer CAR/TCR T-cells limits their functional activity to a short period of time, providing enhanced safety features suited for its deployment in patients with chronic viral diseases.

This approach could be extended to other infectious diseases, including SARS-CoV-2, the virus that causes COVID-19, the authors said.

“We demonstrated that T-cells can be redirected to target the coronavirus responsible for SARS. Our team has now begun exploring the potential of CAR/TCR T-cell immunotherapy for controlling the COVID-19-causing virus, SARS-CoV-2, and protecting patients from its symptomatic effects,” said senior author of the study, Professor Antonio Bertoletti from the Duke-NUS’ EID programme.

Engineered T-cells confer enhanced safety features suited for its deployment in patients with chronic viral diseases. Photo: Journal of Experimental Medicine.

“Infectious diseases remain a leading cause of morbidity and mortality worldwide, necessitating the development of novel and innovative therapeutics. Although immunotherapy is most commonly associated with the treatment of cancer or inflammatory diseases such as arthritis, this commentary accentuates the evolving role of this specialised treatment strategy for various infectious diseases,” said Professor Patrick Casey, senior vice dean for research at Duke-NUS.

The article can be found at: Bertoletti & Tan (2020) Challenges of CAR- and TCR-T cell–based Therapy for Chronic Infections.


Source: Duke-NUS Medical School; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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