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Review
. 2019 Nov 21:10:2711.
doi: 10.3389/fimmu.2019.02711. eCollection 2019.

CAR T Cells Beyond Cancer: Hope for Immunomodulatory Therapy of Infectious Diseases

Michelle Seif  1 , Hermann Einsele  1 , Jürgen Löffler  1
Affiliations
Review

CAR T Cells Beyond Cancer: Hope for Immunomodulatory Therapy of Infectious Diseases

Michelle Seif et al. Front Immunol. .

Abstract

Infectious diseases are still a significant cause of morbidity and mortality worldwide. Despite the progress in drug development, the occurrence of microbial resistance is still a significant concern. Alternative therapeutic strategies are required for non-responding or relapsing patients. Chimeric antigen receptor (CAR) T cells has revolutionized cancer immunotherapy, providing a potential therapeutic option for patients who are unresponsive to standard treatments. Recently two CAR T cell therapies, Yescarta® (Kite Pharma/Gilead) and Kymriah® (Novartis) were approved by the FDA for the treatments of certain types of non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia, respectively. The success of adoptive CAR T cell therapy for cancer has inspired researchers to develop CARs for the treatment of infectious diseases. Here, we review the main achievements in CAR T cell therapy targeting viral infections, including Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus, Human Cytomegalovirus, and opportunistic fungal infections such as invasive aspergillosis.

Keywords: CAR T cells; CMV; HBV; HCV; HIV; infectious diseases; invasive aspergillosis; mAb engineering.

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Figures

Figure 1
Figure 1
CAR T cells targeting infectious diseases. (A) T cells are redirected against HIV by the expression of Env-specific CARs on their surface. Additionally, they are rendered resistant to HIV infection by expression of an anti-fusion peptide. Anti-HIV CAR T cells can successfully kill HIV infected cells and control HIV infection. (B–D) CAR T cells specific for HBV S protein, HCV/E2, or gB can recognize cells infected by HBV, HCV, and CMV, respectively. They can selectively kill the infected cells within the epithelium. (E) Dectin 1-CAR T cells can directly bind to Aspergillus fumigatus germlings and induce hyphal damage. Env, HIV envelope protein; Gp, Glycoprotein; TM, transmembrane; VH, variable heavy chain; gB, Glycoprotein B. Some illustrations were obtained and modified from Servier Medical Art by Servier, licensed under Creative Commons Attribution 3.0 Unported License.
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