Innate and Innate-Like Cells: The Future of Chimeric Antigen Receptor (CAR) Cell Therapy

Cortés-Selva, Diana; Dasgupta, B.; Singh, Sanjaya; Grewal, Iqbal S.

doi:10.1016/j.tips.2020.11.004

Cited by 32 publications

(26 citation statements)

References 97 publications

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“…CAR-T cells engineered to target CD19 can provide curative outcomes for patients with B cell acute lymphoblastic leukemia, with many CAR-T cells targeting different antigens currently in clinical trials [149]. However, there are many reasons why expressing CARs in innate cells may be better than traditional CAR-T cells, including decreased cytokine release storms (CRS) and graft vs. host disease (GvHD) (Figure 2) [150]. iNKT cells have been engineered to express CARs targeting glycolipid and protein antigens.…”

Section: Car-nkt Cellsmentioning

confidence: 99%

“…One potential limitation is that allogenic NKT cells likely express MHC molecules that would be recognized by the recipient as foreign, leading to rejection of the transferred NKT cells. However, strategies to knockout or knockdown MHC on engineered CAR cells could mitigate this [150].…”

Section: Figure 2 Car-nkt Cells Versus Car-t Cells; How Do They Measure Up? Car-nkt Cells Have Several Advantages Over Their Car-t Cell Cmentioning

confidence: 99%

“…Universal CAR-T cells split their T cell signaling unit and antigen targeting domain leaving the CAR-T cell inert until the adaptor protein expressing the antigen targeting domain is added [231]. This may be especially useful for CAR-NKT cells due to their reduced risk of GvHD and CRS, allowing for use of allogenic donors [150]. This opens the option for premade universal CAR-NKT cells and adaptors ready to treat patients, overcoming the lengthy manufacturing process of generating cells from individual patients and allowing more people to receive treatment [232].…”

Section: Car-nkt Cells: Lessons From Car-t Cellsmentioning

confidence: 99%

See 2 more Smart Citations

The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead

Nelson

Lukacs

Johnston

2021

Cancers

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NKT cells are a specialized subset of lipid-reactive T lymphocytes that play direct and indirect roles in immunosurveillance and anti-tumor immunity. Preclinical studies have shown that NKT cell activation via delivery of exogenous glycolipids elicits a significant anti-tumor immune response. Furthermore, infiltration of NKT cells is associated with a good prognosis in several cancers. In this review, we aim to summarize the role of NKT cells in cancer as well as the current strategies and status of NKT cell immunotherapy. This review also examines challenges and future directions for improving the therapy.

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Section: Car-nkt Cellsmentioning

confidence: 99%

Section: Figure 2 Car-nkt Cells Versus Car-t Cells; How Do They Measure Up? Car-nkt Cells Have Several Advantages Over Their Car-t Cell Cmentioning

confidence: 99%

Section: Car-nkt Cells: Lessons From Car-t Cellsmentioning

confidence: 99%

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The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead

Nelson

Lukacs

Johnston

2021

Cancers

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“…While the application of therapeutic Abs has significantly increased the effectiveness of leukemia treatments, other approaches are also emerging with promising healing potential. Current advances in genetic engineering enable CAR transduction in NK cells, macrophages and T cells, thus offering new horizons for cell therapy, although this has been primarily focused on conventional αβ T cells ( 232 , 233 ). In this context, γδ T cells are also undergoing a number of improvements in order to enhance their antitumor capacities.…”

Section: Harnessing γδ T Cells Against Leukemia: From Marrow To Bloodmentioning

confidence: 99%

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

et al. 2021

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Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. γδ T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of γδ T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of γδ T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of γδ T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on γδ T cells in cancer immunotherapy.

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“…γδT cells are primarily distributed in subcutaneous tissue, intestinal mucosa, the respiratory tract, and the urogenital canal [1]. Since they can quickly identify infected and mutated cells, they are considered the first line of defense for "dissidents" inside the human body [2].…”

Section: Introductionmentioning

confidence: 99%

γδT cells: alternative treasure in antitumor immunity

Zhang

Chen

et al. 2022

Explor Immunol

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In recent decades, abundant methods for targeted tumor cell immunotherapy have been developed. It was recently discovered that excellent curative effects observed in hematological tumors cannot be achieved in solid tumors, as serious side effects will occur. These are all derived from engineered adaptive immune cells, the use of which will bring limitations. γδT cells have a unique ability to respond to a variety of tumor cells while linking innate immunity and adaptive immunity, and thus, they are an ideal source of therapeutic allogeneic cells. This review introduces strategies that can optimize the clinical application of γδT cells to provide novel ideas for adoptive immunotherapy in the future.

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Innate and Innate-Like Cells: The Future of Chimeric Antigen Receptor (CAR) Cell Therapy

Cited by 32 publications

References 97 publications

The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead

The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

γδT cells: alternative treasure in antitumor immunity

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