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

Seif, Michelle; Einsele, Hermann; Löffler, Jürgen

doi:10.3389/fimmu.2019.02711

Cited by 94 publications

(62 citation statements)

References 85 publications

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“…The main function of CD8+ T cells is their ability to eliminate foreign cells and agents, making them attractive CAR-Ts for treating infectious diseases [ 16 ]. Patients with chronic hepatitis B virus (HBV) normally do not develop sufficiently strong immune responses, which can lead to the development of liver cancer [ 17 ].…”

Section: Infectious Diseasesmentioning

confidence: 99%

Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections

et al. 2021

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Adoptive cell transfer (ACT) has long been at the forefront of the battle with cancer that began last century with the therapeutic application of tumor-infiltrating lymphocytes (TILs) against melanoma. The development of novel ACT approaches led researchers and clinicians to highly efficient technologies based on genetically engineered T lymphocytes, with chimeric antigen receptor (CAR)-T cells as the most prominent example. CARs consist of an extracellular domain that represents the single-chain variable fragment (scFv) of a monoclonal antibody (mAb) responsible for target recognition and the intracellular domain, which was built from up to several signaling motifs that mediated T cell activation. The number of potential targets amenable for CAR-T cell therapy is expanding rapidly, which means that the tremendous success of this approach in oncology could be further translated to treating other diseases. In this review, we outlined modern trends and recent developments in CAR-T cell therapy from an unusual point of view by focusing on diseases beyond cancer, such as autoimmune disorders and viral infections, including SARS-CoV-2.

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Section: Infectious Diseasesmentioning

confidence: 99%

Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections

et al. 2021

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“…It is currently being investigated for the treatment of viral infections such as HIV-1, HBV, and HCV. Development of CAR-T cells specific to HIV-1 infection has now entered clinical trials ( 195 ).…”

Section: Future Treatmentsmentioning

confidence: 99%

SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment

et al. 2020

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The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002–2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic.

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“…provide in a restricted manner specific antigen binding in a non-major histocompatibility complex (non-MHC) [3]. Theoretically, CAR-T cells can be engineered to target virtually any tumor-associated antigen and, in general, any other antigen, e.g., fungal antigen [4]. improved effector functions and in vivo persistence [8,9].…”

Section: Cars As Recombinant Receptors Transferred In Various T-cell mentioning

confidence: 99%

A brief history of CAR-T cells: from laboratory to the bedside

Styczyński

2020

Acta Haematologica Polonica

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Chimeric antigen receptors (CARs) are genetically engineered receptors that provide specific properties to an immune effector cell and these receptors gain the specificity of a monoclonal antibody targeted against specific tumor cells. T cells with engineered CARs acquire potent immunological properties and redirect the immune system in order to eliminate malignant cells. First-engineered T cells with chimeric molecule (CAR-T cells) were developed in 1989–1993 by Israeli immunologists Zelig Eshhar and Gideon Gross. The first clinical application of CAR-T cells was done in the University of Pennsylvania and Children’s Hospital in Philadelphia by the immunologist Carl June and hematologist David Porter to patients with chronic lymphocytic leukemia in 2011 and together with the pediatrician Stephan Grupp to patients with acute lymphoblastic leukemia (ALL) in 2012. The US Food and Drug Administration Agency (FDA) in 2017 and the European Medicines Agency (EMA) in 2018 have licensed two products of CAR-T cells: tisagenlecleucel for the use in children and young adults up to 25 years of age with B-cell ALL who do not respond to treatment or have relapsed two or more times and tisagenlecleucel and axicabtagene ciloleucel for the use in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Current progress in CAR technology includes the use in other hematological malignancies, solid tumors, the use of dual CAR-T cells and chimeric antigen receptor natural killer cells (CAR-NK cells).

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

Cited by 94 publications

References 85 publications

Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections

Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections

SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment

A brief history of CAR-T cells: from laboratory to the bedside

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