Chimeric Antigen Receptor T-Cells: The Future Is Now

Mchayleh, Wassim; Bedi, Prabhjot Singh; Sehgal, Rajesh; Solh, Melhem

doi:10.3390/jcm8020207

Cited by 24 publications

(21 citation statements)

References 60 publications

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“…This portion of TF is structurally homologous to class II cytokine receptors [17,18]. The extracellular portion of flTF contains two fibronectin type III domains and two disulfide bridges at Cys 49 -Cys 57 and Cys 186 -Cys 209 [19]. Although the extracellular domain of TF is structurally similar to the class II cytokine receptors, it does not bind to any cytokines.…”

Section: Tf Structure and Isoformsmentioning

confidence: 99%

“…A rapidly emerging immunotherapy strategy for treating cancer is chimeric antigen receptor (CAR)-modified T cells (CAR T) [207,208]. To date, CAR T therapy against hematopoietic cancers has met with some success [209], but whether it has real potential against solid tumors is debatable. One limiting factor of CAR T in solid tumors is finding suitable antigens to target [207,208].…”

Section: Tissue Factor As a Target For Cancer Therapymentioning

confidence: 99%

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Beyond thrombosis: the impact of tissue factor signaling in cancer

Unruh

Horbinski

2020

J Hematol Oncol

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Tissue factor (TF) is the primary initiator of the coagulation cascade, though its effects extend well beyond hemostasis. When TF binds to Factor VII, the resulting TF:FVIIa complex can proteolytically cleave transmembrane G protein-coupled proteaseactivated receptors (PARs). In addition to activating PARs, TF:FVIIa complex can also activate receptor tyrosine kinases (RTKs) and integrins. These signaling pathways are utilized by tumors to increase cell proliferation, angiogenesis, metastasis, and cancer stem-like cell maintenance. Herein, we review in detail the regulation of TF expression, mechanisms of TF signaling, their pathological consequences, and how it is being targeted in experimental cancer therapeutics.

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Section: Tf Structure and Isoformsmentioning

confidence: 99%

Section: Tissue Factor As a Target For Cancer Therapymentioning

confidence: 99%

Beyond thrombosis: the impact of tissue factor signaling in cancer

Unruh

Horbinski

2020

J Hematol Oncol

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“…Immunotherapies targeting innate, adaptive immune cells or molecules have demonstrated therapeutic efficacy for a broad range of human malignancies. [1][2][3][4][5] Most recently, immunotherapies targeting the adaptive immune system, specifically, T cells, have improved tumor control. 4 5 Full T-cell activation requires three signals: T-cell receptor (TCR) signaling, costimulatory signaling and cytokine support.…”

Section: Introductionmentioning

confidence: 99%

“…Therapies manipulating TCR signaling, such as chimeric antigen receptor T-cell therapy, are already used in the clinic. 5 Multiple costimulatory pathways can result in the activation of T cells (figure 1). 9 CD80/ CD86-CD28 signaling is a major costimulatory signaling cascade contributing to T-cell activation and cytokine release.…”

Section: Introductionmentioning

confidence: 99%

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T-cell agonists in cancer immunotherapy

Choi

Shi

Haymaker

et al. 2020

J Immunother Cancer

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Cancer cells can evade immune surveillance in the body. However, immune checkpoint inhibitors can interrupt this evasion and enhance the antitumor activity of T cells. Other mechanisms for promoting antitumor T-cell function are the targeting of costimulatory molecules expressed on the surface of T cells, such as 4-1BB, OX40, inducible T-cell costimulator and glucocorticoid-induced tumor necrosis factor receptor. In addition, CD40 targets the modulation of the activation of antigen-presenting cells, which ultimately leads to T-cell activation. Agonists of these costimulatory molecules have demonstrated promising results in preclinical and early-phase trials and are now being tested in ongoing clinical trials. In addition, researchers are conducting trials of combinations of such immune modulators with checkpoint blockade, radiotherapy and cytotoxic chemotherapeutic drugs in patients with advanced tumors. This review gives a comprehensive picture of the current knowledge of T-cell agonists based on their use in recent and ongoing clinical trials.

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Advances in CAR‐Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies

Chen,

Hu,

Mei

2023

Advanced Science

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Chimeric antigen receptor T‐cell (CAR‐T) therapy has emerged as a highly efficacious treatment modality for refractory and relapsed hematopoietic malignancies in recent years. Furthermore, CAR technologies for cancer immunotherapy have expanded from CAR‐T to CAR‐natural killer cell (CAR‐NK), CAR‐cytokine‐induced killer cell (CAR‐CIK), and CAR‐macrophage (CAR‐MΦ) therapy. Nevertheless, the high cost and complex manufacturing processes of ex vivo generation of autologous CAR products have hampered broader application. There is an urgent need to develop an efficient and economical paradigm shift for exploring new sourcing strategies and engineering approaches toward generating CAR‐engineered immune cells to benefit cancer patients. Currently, researchers are actively investigating various strategies to optimize the preparation and sourcing of these potent immunotherapeutic agents. In this work, the latest research progress is summarized. Perspectives on the future of CAR‐engineered immune cell manufacturing are provided, and the engineering approaches, and diverse sources used for their development are focused upon.

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Chimeric Antigen Receptor T-Cells: The Future Is Now

Cited by 24 publications

References 60 publications

Beyond thrombosis: the impact of tissue factor signaling in cancer

Beyond thrombosis: the impact of tissue factor signaling in cancer

T-cell agonists in cancer immunotherapy

Advances in CAR‐Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies

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