Chimeric Antigen Receptors Targeting Human Cytomegalovirus

Area of Science:

• Immunology
• Virology
• Biotechnology

Background:

• Human cytomegalovirus (CMV) is a widespread virus causing severe illness in immunocompromised individuals.
• Adoptive T-cell therapy shows promise but requires scalable methods for broad application.
• Chimeric antigen receptor (CAR) technology offers a potential platform for engineered T-cell therapies.

Purpose of the Study:

• To develop and evaluate novel CARs targeting human cytomegalovirus (CMV).
• To identify a lead CAR construct for potential therapeutic development against CMV infections.

Main Methods:

• Generated eight novel CARs using anti-CMV neutralizing antibody sequences.
• Transduced CARs into primary CD8+ T cells via lentiviral vectors.
• Assessed CAR T-cell activity through cytokine release, degranulation, proliferation, cytolysis, and viral suppression assays.

Main Results:

• All eight novel CARs were successfully expressed in CD8+ T cells.
• CAR T-cell functions varied, with one CAR (21E9-based) consistently outperforming others.
• The 21E9-based CAR demonstrated superior cytokine release, degranulation, proliferation, cytolysis of infected cells, and viral suppression.

Conclusions:

• A novel CMV-specific CAR, particularly the 21E9-based construct, shows significant therapeutic potential.
• This CAR T-cell approach offers a promising strategy for treating CMV infections.
• The findings support further development of CMV-targeted CAR immunotherapies for clinical application.