Design of Switchable Chimeric Antigen Receptor T Cells Targeting Breast Cancer

Cao, Yu; Rodgers, David T.; Du, Juanjuan; Ahmad, Insha; Hampton, Eric; Jennifer, S. Y.; Mazagova, Magdalena; Choi, Sei-hyun; Yun, Hwa Young; Xiao, Han; Yang, Pengyu; Luo, Xiaozhou; Lim, Reyna K. V.; Pugh, Holly; Wang, Feng; Kazane, Stephanie A.; Wright, Timothy M.; Kim, Chan Hyuk; Schultz, Peter G.; Young, Travis S.

doi:10.1002/anie.201601902

Cited by 99 publications

(78 citation statements)

References 31 publications

(25 reference statements)

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“…While treatments for the cytokine storm do exist, psychiatrists can play an integral role in managing the distress that can occur when patients are in a delirium and experiencing altered mental status and potential psychoses. Given the success rates in providing remission for patients with treatment-refractory acute lymphoblastic leukemia, CAR T-cell studies have begun for a number of other cancer types, including chronic lymphocytic leukemia, acute myeloid leukemia, multiple myeloma, prostate cancer, and breast cancer (Giordano et al, 2011; Ritchie et al, 2013; Deng et al, 2015; Porter et al, 2015; Cao et al, 2016; Drent et al, 2016). It is therefore expected that neurotoxicity will be found at greater rates, which may lead to increased routine integration of psychiatry, in addition to neurology, to assist in symptom management.…”

Section: Discussionmentioning

confidence: 99%

Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia

Prudent

Breitbart

2017

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Chimeric antigen receptor T cells are used in the treatment of B-cell leukemias. Common chimeric antigen receptor T-cell toxicities can range from mild flu-like symptoms, such as fever and myalgia, to a more striking neuropsychiatric toxicity that can present as discrete neurological symptoms and delirium. We report here two cases of chimeric antigen receptor T-cell neuropsychiatric toxicity, one who presented as a mild delirium and aphasia that resolved without intervention, and one who presented with delirium, seizures, and respiratory insufficiency requiring intensive treatment. The current literature on the treatment and proposed mechanisms of this clinically challenging chimeric antigen receptor T-cell complication is also presented.

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Section: Discussionmentioning

confidence: 99%

Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia

Prudent

Breitbart

2017

Pall Supp Care

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“…3b) 78,79 . Rather than recognizing an antigen, the sCAR binds to a bioorthogonal tag placed on a Fab derived from a mAb such as Herceptin.…”

Section: Review Articlementioning

confidence: 99%

Programming CAR-T cells to kill cancer

2018

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T cells engineered to express chimeric antigen receptors (CARs) that are specific for tumour antigens have led to high complete response rates in patients with haematologic malignancies. Despite this early success, major challenges to the broad application of CAR-T cells as cancer therapies remain, including treatment-associated toxicities and cancer relapse with antigen-negative tumours. Targeting solid tumours with CAR-T cells poses additional obstacles because of the paucity of tumourspecific antigens and the immunosuppressive effects of the tumour microenvironment. To overcome these challenges, T cells can be programmed with genetic modules that increase their therapeutic potency and specificity. In this Review Article, we survey major advances in the engineering of next-generation CAR-T therapies for haematologic cancers and solid cancers, with particular emphasis on strategies for the control of CAR specificity and activity and on approaches for improving CAR-T-cell persistence and overcoming immunosuppression. We also lay out a roadmap for the development of off-the-shelf CAR-T cells.

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“…Aiming to specifically control CAR T-cell activity toward the antigen, several models of adapter-mediated CARs, also known as universal CARs, have been developed (62)(63)(64)(65)(66)(67)(68)(69)(70)(71). A shared feature is their method of tumor recognition, which is achieved by linking an adaptor, a molecule recognized by the CAR, to an antibody or ligand that recognizes the tumor antigen.…”

Section: Adapter Mediated Carsmentioning

confidence: 99%

Emerging Approaches for Regulation and Control of CAR T Cells: A Mini Review

et al. 2020

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Chimeric antigen receptor (CAR) T cells have emerged as a promising treatment for patients with advanced B-cell cancers. However, widespread application of the therapy is currently limited by potentially life-threatening toxicities due to a lack of control of the highly potent transfused cells. Researchers have therefore developed several regulatory mechanisms in order to control CAR T cells in vivo. Clinical adoption of these control systems will depend on several factors, including the need for temporal and spatial control, the immunogenicity of the requisite components as well as whether the system allows reversible control or induces permanent elimination. Here we describe currently available and emerging control methods and review their function, advantages, and limitations.

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Design of Switchable Chimeric Antigen Receptor T Cells Targeting Breast Cancer

Cited by 99 publications

References 31 publications

Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia

Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia

Programming CAR-T cells to kill cancer

Emerging Approaches for Regulation and Control of CAR T Cells: A Mini Review

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