Novel approach may provide longer-term immunity against COVID and new variants, as well as a useful alternative for patients who respond poorly to conventional vaccines
In an exciting potential advance in the war against COVID-19, Drs. Christopher E. Rudd, Uri H. Saragovi and colleagues have published a paper in iScience describing the first successful design of chimeric antigen receptors on T-cells (called CAR-Ts) that recognize and kill cells expressing SARs CoV 2 virus (COVID-19) spike peptides in mice. In recent years, CAR-T cell therapy has been developed and used as an effective immunotherapy against cancers, and hematological cancers in particular.
It consists of collecting T lymphocytes, a type of white blood cells of the immune system that play a key role in shaping the adaptive immune response, from a patient. These T cells are then genetically multiplied and modified to recognize and destroy cancer cells, and reinjected into the patient.
“Our study is among the first to explore the feasibility of anti-SARS-CoV-2 CAR-T immunotherapy and its potential to prevent and treat severe cases of COVID-19,” says Dr. Uri H. Saragovi, Senior Investigator at the Lady Davis Institute (LDI) at the Jewish General Hospital and member of the McGill Center for Translational Research in Cancer based at the Segal Cancer Centre. “One big advantage is that CAR-Ts have the potential to provide longer term immunity to COVID-19 than most vaccines. Against cancer, for example, CAR-Ts can remain in patients for up to two years.”
The study used antibodies against the spike protein of SARs CoV2 to generate CAR-Ts and showed that the CAR-Ts react effectively, killing target cells in mice. “Actually, we were surprised by how effective the approach was and how avid the CAR-Ts are in attacking targets expressing SAR COV2 peptides, “ says Dr. Christopher E. Rudd, Chief of the Immunology-Oncology Axis at the Hôpital Maisonneuve-Rosemont Research Centre, Adjunct Professor in the Department of Medicine at McGill University, and member of the McGill Center for Translational Research in Cancer, who led the study. “As many as 10 CAR-Ts form around a single target cell, which has no chance of surviving such an attack. Ours is the first step in the development of a new therapeutic approach against the SARs CoV2 virus.”
Present strategies use vaccines to provide an antibody response, and to varying degrees, a T-cell response. However, a significant number of vaccinated people respond sub-optimally. This includes older or frail adults, people who are immunocompromised, those treated for certain types of cancer or who take certain medications, etc. Furthermore, the long-term efficacy of the antibodies induced by the vaccines and their overall resistance to new variants remain unclear, pointing to the need for new, alternate or complementary therapeutic approaches, such as CAR-T cell therapy.
“We have designed T-cells that can directly target the spike protein of SARs CoV2 and which eliminate cells in vivo that express peptides from the SARs CoV2 virus,” restates Dr. Rudd. “The success of these cells will not depend on whether someone can respond to a vaccine. Rather, we are providing the ‘armed T-cells’ ready to do the job even in people who otherwise cannot mount a good immune response.”
As such, COVID-19 CAR-Ts may provide longer-term immunity than seen with present vaccine approaches and could be useful in complementing vaccine approaches for patients that respond poorly to conventional vaccines especially in the case of immunocompromised patients.
Although the present study is currently limited to mice, “the CAR-T approach is the first step in developing a new potential weapon in our battery of approaches to defeat the SARs CoV2 virus and new variants,” explains Dr. Rudd. “Further work is needed to assess the ability of our CAR-T approach in eliminating different viral infections and the potential for secondary effects. We also need to generate a larger cohort of CARs that react with other sites of the COVID virus. The recognition of more sites will produce a broader and more complete response.”
Guo, X., Kazanova, A., Thurmond, S., Saragovi, H.U., Rudd, C.E, Effective chimeric antigen receptor T-cells (CAR-Ts) against SARS-CoV-2 ISCIENCE (2021), doi: https://doi.org/10.1016/j.isci.2021.103295
