CAR-T approach boosts the immune response of T lymphocytes to COVID-19
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
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