A close look at current γδ T-cell immunotherapy

Li, Ma; Yang, Feng; Zhou, Zishan

doi:10.3389/fimmu.2023.1140623

Cited by 11 publications

(10 citation statements)

References 116 publications

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“…Although most of these nodes failed to be distinct in CD4 + T cell compartment (Figure 7A; right panel & 7C), nodes 16, 22 and 30 showed significant abundance in adult participant's gd T cell compartment (Figure 7B; right panel & 7D). Consistent with previous report 59 , gd T cells exist as heterogeneous populations with distinct properties. Taken together, these data indicate that the functional plasticity of the gd T cells is influenced by age and stimulus type.…”

Section: Tlr7/8a-mediated Unique Abundance Of Ifnγ Producing Gd T Cel...supporting

confidence: 93%

Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro

Dowling,

Schüller,

Barman

et al. 2023

Preprint

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Vaccination reduces morbidity and mortality due to infections, but efficacy may be limited due to distinct immunogenicity at the extremes of age. This raises the possibility of employing adjuvants to enhance immunogenicity and protection. Early IFNγ production is a hallmark of effective vaccine immunogenicity in adults serving as a biomarker that may predict effective adjuvanticity. We utilized mass cytometry (CyTOF) to dissect the source of adjuvant-induced cytokine production in human blood mononuclear cells (BMCs) from newborns (~39-week-gestation), adults (~18-63 years old) and elders (>65 years of age) after stimulation with pattern recognition receptors agonist (PRRa) adjuvants. Dimensionality reduction analysis of CyTOF data mapped the BMC compartment, elucidated age-specific immune responses and profiled PRR-mediated activation of monocytes and DCs upon adjuvant stimulation. Furthermore, we demonstrated PRRa adjuvants mediated innate IFNγ induction and mapped NK cells as the key source of TLR7/8 agonist (TLR7/8a) specific innate IFNγ responses. Hierarchical clustering analysis revealed age and TLR7/8a-specific accumulation of innate IFNγ producing γδ T cells. Our study demonstrates the application of mass cytometry and cutting-edge computational approaches to characterize immune responses across immunologically distinct age groups and may inform identification of the bespoke adjuvantation systems tailored to enhance immunity in distinct vulnerable populations.

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Section: Tlr7/8a-mediated Unique Abundance Of Ifnγ Producing Gd T Cel...supporting

confidence: 93%

Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro

Dowling,

Schüller,

Barman

et al. 2023

Preprint

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“…Strategies to utilize γδ T cells for cancer immunotherapy are summarized in recent reviews ( 56 – 59 ). These include the activation or stimulation of endogenous γδ T cells via exogenous aminobisphosphonates and anti-CD3/anti-tumor antigen bispecific antibodies as well as ex vivo expansion of peripheral blood-derived γδ T cells ( 60 ).…”

Section: Harnessing γδ T Cells For Anti-tumor Immunotherapymentioning

confidence: 99%

Gamma/delta T cells as cellular vehicles for anti-tumor immunity

Wang,

Lim,

Tan

2024

Front. Immunol.

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Adoptive cellular immunotherapy as a new paradigm to treat cancers is exemplified by the FDA approval of six chimeric antigen receptor-T cell therapies targeting hematological malignancies in recent years. Conventional αβ T cells applied in these therapies have proven efficacy but are confined almost exclusively to autologous use. When infused into patients with mismatched human leukocyte antigen, αβ T cells recognize tissues of such patients as foreign and elicit devastating graft-versus-host disease. Therefore, one way to overcome this challenge is to use naturally allogeneic immune cell types, such as γδ T cells. γδ T cells occupy the interface between innate and adaptive immunity and possess the capacity to detect a wide variety of ligands on transformed host cells. In this article, we review the fundamental biology of γδ T cells, including their subtypes, expression of ligands, contrasting roles in and association with cancer prognosis or survival, as well as discuss the gaps in knowledge pertaining to this cell type which we currently endeavor to elucidate. In addition, we propose how to harness the unique properties of γδ T cells for cellular immunotherapy based on lessons gleaned from past clinical trials and provide an update on ongoing trials involving these cells. Lastly, we elaborate strategies that have been tested or can be explored to improve the anti-tumor activity and durability of γδ T cells in vivo.

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“…Another T cell subtype, γδT cells, have been highly favored recently, owing to the fact that they do not contribute to GVHD. [ 58 ] Donor‐derived γδT cells utilize their intrinsic receptors to recognize a variety of tumor antigens in a histocompatibility complex (MHC) in an independent manner, allowing their application in an allogeneic setting without the need for TCR depletion. Furthermore, upon activation, they can elicit adaptive immune responses.…”

Section: Third Party‐derived Car‐engineered Immune Cellsmentioning

confidence: 99%

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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A close look at current γδ T-cell immunotherapy

Cited by 11 publications

References 116 publications

Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro

Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro

Gamma/delta T cells as cellular vehicles for anti-tumor immunity

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

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