CARTs for Solid Tumors: Feasible or Infeasible?

Li, Wei; Song, Xiujun; Jin, Yu; Li, Fengsheng; Yu, Huijie; Cao, Cheng; Jiang, Qisheng

doi:10.1159/000477095

Cited by 5 publications

(2 citation statements)

References 93 publications

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“…For treating B-cell malignancies, the second and third-generation CAR T cells have gained much success [14,33], but its efficacy to treat solid tumors still remains insufficient [3,4,34], particularly due to poor proliferation and survival of CAR T cells in vivo. NKG2D-based CAR T cells for immunotherapies have been reported to be promising for targeting NKG2D ligand-positive cancers [11,35].…”

Section: Discussionmentioning

confidence: 99%

Co-Expression of IL-7 Improves NKG2D-Based CAR T Cell Therapy on Prostate Cancer by Enhancing the Expansion and Inhibiting the Apoptosis and Exhaustion

Ying

et al. 2020

Cancers

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Chimeric antigen receptor (CAR) T-cell therapy is a promising approach in treating solid tumors but the therapeutic effect is limited. Prostate cancer is a typical solid malignancy with invasive property and a highly immunosuppressive microenvironment. Ligands for the NKG2D receptor are primarily expressed on many cancer cells, including prostate cancer. In this study, we utilized NKG2D-based CAR to treat prostate cancer, and improved the therapeutic effect by co-expression of IL-7. The results showed that NKG2D-CAR T cells performed significantly increased cytotoxicity against prostate cancer compared to non-transduced T cells in vitro and in vivo. Moreover, the introduction of the IL-7 gene into the NKG2D-CAR backbone enhanced the production of IL-7 in an antigen-dependent manner. NKG2DIL7-CAR T cells exhibited better antitumor efficacy at 16 h and 72 h in vitro, and inhibited tumor growth in xenograft models more effectively. In mechanism, enhanced proliferation and Bcl-2 expression in CD8+ T cells, decreased apoptosis and exhaustion, and increased less-differentiated cell phenotype may be the reasons for the improved persistence and survival of NKG2DIL7-CAR T cells. In conclusion, these findings demonstrated that NKG2D is a promising option for CAR T-cell therapy on prostate cancer, and IL-7 has enhanced effect on NKG2D-based CAR T-cell immunotherapy, providing a novel adoptive cell therapy for prostate cancer either alone or in combination with IL-7.

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Section: Discussionmentioning

confidence: 99%

Co-Expression of IL-7 Improves NKG2D-Based CAR T Cell Therapy on Prostate Cancer by Enhancing the Expansion and Inhibiting the Apoptosis and Exhaustion

Ying

et al. 2020

Cancers

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“…The immune-suppressive characteristics of solid tumors, which arise due to the presentation of checkpoint inhibitory ligands and metabolites from diverse metabolic pathways collectively create a tumor microenvironment (TME). This microenvironment makes it exceedingly challenging for CAR-T cells to infiltrate and effectively eliminate solid tumors, leading to significant barriers to CAR-T cell therapy’s success [ 22 ]. Adrenergic stress is one of the culprits, among others, responsible for immunosuppression inside the TME.…”

Section: Introductionmentioning

confidence: 99%

β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy

Farooq

Ajmal

Hui

et al. 2023

IJMS

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The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of the tumor microenvironment, nor-adrenaline (NA) is poured in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surfaces of cancer and immune cells and are often involved in the activation of pro-tumoral signaling pathways. Beta2-adrenergic receptors (β2-ARs) are an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate regulatory immune cells and inhibit effector immune cells. Blocking β2-AR increases activation, proliferation, and cytokine release of T lymphocytes. Moreover, β2-AR deficiency during metabolic reprogramming of T cells increases mitochondrial membrane potential and biogenesis. In the view of the available research data, the immunosuppressive role of β2-AR in T cells presents it as a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged the contemporary knowledge about adrenergic-stress-mediated β2-AR activation on T lymphocytes inside tumor milieu.

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Anti-mesothelin CAR-T immunotherapy in patients with ovarian cancer

Chen

et al. 2022

Cancer Immunol Immunother

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CARTs for Solid Tumors: Feasible or Infeasible?

Cited by 5 publications

References 93 publications

Co-Expression of IL-7 Improves NKG2D-Based CAR T Cell Therapy on Prostate Cancer by Enhancing the Expansion and Inhibiting the Apoptosis and Exhaustion

Co-Expression of IL-7 Improves NKG2D-Based CAR T Cell Therapy on Prostate Cancer by Enhancing the Expansion and Inhibiting the Apoptosis and Exhaustion

β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy

Anti-mesothelin CAR-T immunotherapy in patients with ovarian cancer

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