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Chimeric Antigen Receptors Targeting Human Cytomegalovirus
- Source :
- The Journal of infectious diseases, vol 222, iss 5, J Infect Dis
- Publication Year :
- 2020
- Publisher :
- eScholarship, University of California, 2020.
-
Abstract
- Human cytomegalovirus (CMV) is a ubiquitous pathogen that causes significant morbidity in some vulnerable populations. Individualized adoptive transfer of ex vivo expanded CMV-specific CD8+ T cells has provided proof-of-concept that immunotherapy can be highly effective, but a chimeric antigen receptor (CAR) approach would provide a feasible method for broad application. We created 8 novel CARs using anti-CMV neutralizing antibody sequences, which were transduced via lentiviral vector into primary CD8+ T cells. All CARs were expressed. Activity against CMV-infected target cells was assessed by release of cytokines (interferon-γ and tumor necrosis factor–α), upregulation of surface CD107a, proliferation, cytolysis of infected cells, and suppression of viral replication. While some CARs showed varying functional activity across these assays, 1 CAR based on antibody 21E9 was consistently superior in all measures. These results support development of a CMV-specific CAR for therapeutic use against CMV and potentially other applications harnessing CMV-driven immunotherapies.
- Subjects :
- 0301 basic medicine
Human cytomegalovirus
Adoptive cell transfer
medicine.medical_treatment
Adoptive
Cytomegalovirus
CD8-Positive T-Lymphocytes
Antibodies, Viral
Virus Replication
Immunotherapy, Adoptive
Medical and Health Sciences
Transduction, Genetic
Receptors
Immunology and Allergy
Viral
Neutralizing antibody
Neutralizing
Cancer
Receptors, Chimeric Antigen
chimeric antigen receptor
virus diseases
Gene Therapy
Biological Sciences
Infectious Diseases
5.1 Pharmaceuticals
Immunotherapy
Antibody
Development of treatments and therapeutic interventions
Infection
Biotechnology
030106 microbiology
cellular immunity
Biology
Microbiology
Antibodies
Viral vector
Vaccine Related
Major Articles and Brief Reports
03 medical and health sciences
Transduction
Genetic
medicine
Genetics
Humans
Cell Proliferation
5.2 Cellular and gene therapies
Chimeric Antigen
medicine.disease
Antibodies, Neutralizing
Virology
Chimeric antigen receptor
030104 developmental biology
HEK293 Cells
Good Health and Well Being
human cytomegalovirus
biology.protein
Immunization
CD8
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- The Journal of infectious diseases, vol 222, iss 5, J Infect Dis
- Accession number :
- edsair.doi.dedup.....25f77f3cddd458b2234fd571c8849cde