TGF-β/IL-7 Chimeric Switch Receptor-Expressing CAR-T Cells Inhibit Recurrence of CD19-Positive B Cell Lymphoma

Noh, Kyung-Eun; Lee, Jun-Ho; Choi, So-Yeon; Jung, Nam-Chul; Nam, Ji-Hee; Oh, Ji-Soo; Song, Jie‐Young; Seo, Han Geuk; Wang, Yu; Lee, Hyun Soo; Lim, Dae‐Seog

doi:10.3390/ijms22168706

Cited by 27 publications

(14 citation statements)

References 45 publications

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“…134,135 Switch receptors are modular with their inputs and outputs, and multiple designs have been developed targeting other ligands such as Fas, fusing FasR to 4-1BB intracellular signaling domains, 136 or targeting immunosuppressive cytokines such as the GM-CSF/IL-18 switch receptors, 137 or even a TGFβ/IL-7. 138 In cases where these enhancements can conform to the cargo capacity of cell therapies, they equip the graft with additional capabilities to overcome multiple suppressive mechanisms. However, not all tumors engage the same immunosuppressive mechanisms so we must design the graft with the correct tools to overcome the TME we are hoping to treat.…”

Section: Engineering Complementary Mechanisms Into T Cellsmentioning

confidence: 99%

“…These receptors bind to PD‐L1, which is highly expressed in suppressive tumor microenvironments, and boost activating T‐cell signaling rather than dampen it 134,135 . Switch receptors are modular with their inputs and outputs, and multiple designs have been developed targeting other ligands such as Fas, fusing FasR to 4‐1BB intracellular signaling domains, 136 or targeting immunosuppressive cytokines such as the GM‐CSF/IL‐18 switch receptors, 137 or even a TGFβ/IL‐7 138 . In cases where these enhancements can conform to the cargo capacity of cell therapies, they equip the graft with additional capabilities to overcome multiple suppressive mechanisms.…”

Section: Principle 5: Designing Multi‐nodal Approaches For Tumor Erad...mentioning

confidence: 99%

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Toward the clinical development of synthetic immunity to cancer

Garcia

Burnett

Roybal

2023

Immunological Reviews

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SummarySynthetic biology (synbio) tools, such as chimeric antigen receptors (CARs), have been designed to target, activate, and improve immune cell responses to tumors. These therapies have demonstrated an ability to cure patients with blood cancers. However, there are significant challenges to designing, testing, and efficiently translating these complex cell therapies for patients who do not respond or have immune refractory solid tumors. The rapid progress of synbio tools for cell therapy, particularly for cancer immunotherapy, is encouraging but our development process should be tailored to increase translational success. Particularly, next‐generation cell therapies should be rooted in basic immunology, tested in more predictive preclinical models, engineered for potency with the right balance of safety, educated by clinical findings, and multi‐faceted to combat a range of suppressive mechanisms. Here, we lay out five principles for engineering future cell therapies to increase the probability of clinical impact, and in the context of these principles, we provide an overview of the current state of synbio cell therapy design for cancer. Although these principles are anchored in engineering immune cells for cancer therapy, we posit that they can help guide translational synbio research for broad impact in other disease indications with high unmet need.

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Section: Engineering Complementary Mechanisms Into T Cellsmentioning

confidence: 99%

Section: Principle 5: Designing Multi‐nodal Approaches For Tumor Erad...mentioning

confidence: 99%

Toward the clinical development of synthetic immunity to cancer

Garcia

Burnett

Roybal

2023

Immunological Reviews

View full text Add to dashboard Cite

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“…In vitro, it showed lower levels of SAMD2 phosphorylation and stronger target-specific cytotoxicity than the control CAR-T cells. In tumor-tolerant mouse models, overall survival and relapse-free survival were significantly longer in mice treated with CD19 CAR-Ttri-I7R-T cells than in control mice, providing a novel strategy for B cell lymphoma treatment [ 127 ]. All the above studies have shown that CAR-T cells expressing IL-7R can effectively kill specific cancer cells, crossing boundaries of traditional CAR-T cells in solid tumors, and provide a new strategy for cancer treatment.…”

Section: Application Of Il-7 and Il-7r In Cancer Immunotherapymentioning

confidence: 99%

The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy

Wang

Kong

Kim

et al. 2022

IJMS

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Interleukin-7 (IL-7) is a multipotent cytokine that maintains the homeostasis of the immune system. IL-7 plays a vital role in T-cell development, proliferation, and differentiation, as well as in B cell maturation through the activation of the IL-7 receptor (IL-7R). IL-7 is closely associated with tumor development and has been used in cancer clinical research and therapy. In this review, we first summarize the roles of IL-7 and IL-7Rα and their downstream signaling pathways in immunity and cancer. Furthermore, we summarize and discuss the recent advances in the use of IL-7 and IL-7Rα as cancer immunotherapy tools and highlight their potential for therapeutic applications. This review will help in the development of cancer immunotherapy regimens based on IL-7 and IL-7Rα, and will also advance their exploitation as more effective and safe immunotherapy tools.

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“…CAR-T cell therapy has essentially reformed the therapeutic regimen of hematological malignancies (156). By constructing novel CD19 CAR-tTRII-I7R-T cells, which convert the TGF-b signaling into immuneactivating IL-7 signaling, the tumor-killing efficacy of modified CAR-T cells was significantly better than in the control group (157). The above studies proposed that TGF-b signaling prohibition could be a potential therapeutic approach for relieving defects in hematopoiesis.…”

Section: Preclinical Studies Targeting Tgf-b As a Cancer Therapymentioning

confidence: 99%

The Love-Hate Relationship Between TGF-β Signaling and the Immune System During Development and Tumorigenesis

Zheng

Mu²,

Zhang³

et al. 2022

Front. Immunol.

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Since TGF-β was recognized as an essential secreted cytokine in embryogenesis and adult tissue homeostasis a decade ago, our knowledge of the role of TGF-β in mammalian development and disease, particularly cancer, has constantly been updated. Mounting evidence has confirmed that TGF-β is the principal regulator of the immune system, as deprivation of TGF-β signaling completely abrogates adaptive immunity. However, enhancing TGF-β signaling constrains the immune response through multiple mechanisms, including boosting Treg cell differentiation and inducing CD8+ T-cell apoptosis in the disease context. The love-hate relationship between TGF-β signaling and the immune system makes it challenging to develop effective monotherapies targeting TGF-β, especially for cancer treatment. Nonetheless, recent work on combination therapies of TGF-β inhibition and immunotherapy have provide insights into the development of TGF-β-targeted therapies, with favorable outcomes in patients with advanced cancer. Hence, we summarize the entanglement between TGF-β and the immune system in the developmental and tumor contexts and recent progress on hijacking crucial TGF-β signaling pathways as an emerging area of cancer therapy.

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TGF-β/IL-7 Chimeric Switch Receptor-Expressing CAR-T Cells Inhibit Recurrence of CD19-Positive B Cell Lymphoma

Cited by 27 publications

References 45 publications

Toward the clinical development of synthetic immunity to cancer

Toward the clinical development of synthetic immunity to cancer

The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy

The Love-Hate Relationship Between TGF-β Signaling and the Immune System During Development and Tumorigenesis

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