Clin Transl Immunol: Using cancer immunotherapy technology to develop immunotherapies with the potential to treat SARS-CoV-2 infection

Millions of deaths from SARS-CoV-2 infection and millions more continue to experience the long-term after-effects of COVID (Long COVID) make the discovery of practical, accessible, and robust SARS-CoV-2 prevention measures and treatments for COVID-19 critical
.

In a new study, Dr.
Derya Unutmaz and his research team at the Jackson Genomic Medicine Laboratory in the United States used CAR-T cell therapy, commonly used in cancer treatment, to eliminate the SARS-CoV-2 virus
.
They demonstrate several immunization-based strategies to explore the treatment and prevention
of COVID-19.
The findings were recently published in the journal Clinical & Translational Immunology in the paper "Targeting SARS-CoV-2 infection through CAR-T-like bispecific T cell engagers incorporating ACE2.
"

The first immunotherapy focused on the spike protein present on the surface of the SARS-CoV-2 virus and the receptor angiotensin-converting enzyme 2 (ACE2)
on the surface of host cells.
This spike protein is responsible for infecting healthy host cells
.
The protein enters the host cell via the ACE2 receptor, allowing the virus's RNA to begin taking over it
.
In the new study, T cells were genetically engineered to become anti-spike protein and ACE2-resistant CAR-T cells, targeting spike proteins, or ACE2 receptors, with high specificity and efficiency
in multiple infected cell types.

The second immunotherapy provides an antibody-based means
of preventing SARS-CoV-2 infection.
T cells are genetically engineered to express a bispecific antibody fused with ACE2 to activate the patient's own T cells and destroy host cells
that present the SARS-CoV-2 spike protein on the cell surface after infection.
Instead of having cells outside the body genetically engineered to kill infected cells, this ACE2-bispecific antibody therapy activates healthy T cells in the individual to target host cells
that present the SARS-CoV-2 spike protein after infection.

Human primary CD8 T cells were genetically engineered to express CAR molecules
targeting host cells presenting the SARS-CoV-2 spike protein.
Image from Clinical & Translational Immunology, 2022, doi:10.
1002/cti2.
1421
.

Unlike most current treatments, cells expressing this ACE2-bispecific antibody take advantage of the ACE2 receptor to target different manifestations of the spike protein in all SARS-CoV-2 variants
, including the Delta variant and the Omicron variant.
Therefore, this ACE2-bispecific antibody therapy can more effectively eliminate SARS-CoV-2 variants
that bind more strongly to ACE2.
It can also serve as a bait to stop the virus from entering host cells, providing a potential prevention strategy
.

Both this CAR-T cell therapy against COVID-19 and this ACE2-bispecific antibody-based therapy offer promising potential strategies
for future COVID-19 treatment and prevention.
(Biovalley Bioon.
com)

Resources:

Mikail Dogan et al.
 Targeting SARS-CoV-2 infection through CAR-T-like bispecific T cell engagers incorporating ACE2, Clinical & Translational Immunology, 2022, doi:10.
1002/cti2.
1421.