Anti‐IL‐7 receptor α monoclonal antibody (GSK2618960) in healthy subjects – a randomized, double‐blind, placebo‐controlled study

Ellis, Joanne; Maurik, André van; Fortunato, Léa; Gisbert, Sophie; Chen, Keguan; Schwartz, Ann; McHugh, SM; Want, Andrew; Franco, Sara Santos; Oliveira, Joao-Joaquim; Price, Jeffrey; Coles, Alasdair; Brown, Kim; Su, Donggang; Craigen, Jenny; Yang, Jiansong; Brett, Sara; Davis, Bill; Cheriyan, Joseph; Kousin-Ezewu, Onajite; Gray, Frank; Thompson, Paul; Fernando, Disala

doi:10.1111/bcp.13748

Cited by 38 publications

(36 citation statements)

References 42 publications

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“…The expression of IL-4, a classic marker for Th2 cells, is increased by IL-7 and is a direct cause of edema (45,46). This cytokine's activity is targeted for diseases related to pathogenic T-cells (47). Th2 cells express both CCR3 and CCR4 receptors that bind chemokines to direct their migration to the site of injury or infection (48,49).…”

Section: Discussionmentioning

confidence: 99%

Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke

et al. 2020

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“…Accordingly, targeting IL7Rα using specific antibodies may also affect T cells 53 and lead to immunodeficiency in patients. However, a recent study showed that treating healthy subjects with anti-human IL7R antibody was well tolerated and did not result in obvious alterations in immune cell populations and inflammatory cytokine profiles 54 . Thus, treatment with anti-IL7R antibodies might provide a key therapeutic approach especially for TKI-resistant ALL once the different antibodies are characterized regarding their side-effects and compared with standard chemotherapy in appropriate clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Synergism between IL7R and CXCR4 drives BCR-ABL induced transformation in Philadelphia chromosome-positive acute lymphoblastic leukemia

et al. 2020

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Ph + acute lymphoblastic leukemia (ALL) is characterized by the expression of an oncogenic fusion kinase termed BCR-ABL1. Here, we show that interleukin 7 receptor (IL7R) interacts with the chemokine receptor CXCR4 to recruit BCR-ABL1 and JAK kinases in close proximity. Treatment with BCR-ABL1 kinase inhibitors results in elevated expression of IL7R which enables the survival of transformed cells when IL7 was added together with the kinase inhibitors. Importantly, treatment with anti-IL7R antibodies prevents leukemia development in xenotransplantation models using patient-derived Ph + ALL cells. Our results suggest that the association between IL7R and CXCR4 serves as molecular platform for BCR-ABL1-induced transformation and development of Ph + ALL. Targeting this platform with anti-IL7R antibody eliminates Ph + ALL cells including those with resistance to commonly used ABL1 kinase inhibitors. Thus, anti-IL7R antibodies may provide alternative treatment options for ALL in general and may suppress incurable drug-resistant leukemia forms.

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“…This represents an important drawback, as potential therapeutic benefits may be counteracted by associated off-target toxicities and severe combined immunodeficiency [ 256 ]. Nevertheless, recent studies suggest that immunosuppression induced by treatment of mouse autoimmune arthritis with an anti-IL-7Rα ADC could be well tolerated clinically for a period of time [ 257 ], and very promising results have been reported from anti-IL-7R mAb clinical trials for autoimmune diseases [ 258 ]. Overall, current information on the major contribution of normal IL-7R signaling to the onset, maintenance, and progression of acute leukemias opens a new and major area of research to develop and validate novel therapies focusing on the IL-7R pathway.…”

Section: Potential New Targets For T-all Immunotherapymentioning

confidence: 99%

Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia

Bayón-Calderón

Toribio

González-García

2020

IJMS

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T-cell acute lymphoblastic leukemia (T-ALL), a T-cell malignant disease that mainly affects children, is still a medical challenge, especially for refractory patients for whom therapeutic options are scarce. Recent advances in immunotherapy for B-cell malignancies based on increasingly efficacious monoclonal antibodies (mAbs) and chimeric antigen receptors (CARs) have been encouraging for non-responding or relapsing patients suffering from other aggressive cancers like T-ALL. However, secondary life-threatening T-cell immunodeficiency due to shared expression of targeted antigens by healthy and malignant T cells is a main drawback of mAb—or CAR-based immunotherapies for T-ALL and other T-cell malignancies. This review provides a comprehensive update on the different immunotherapeutic strategies that are being currently applied to T-ALL. We highlight recent progress on the identification of new potential targets showing promising preclinical results and discuss current challenges and opportunities for developing novel safe and efficacious immunotherapies for T-ALL.

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Anti‐IL‐7 receptor α monoclonal antibody (GSK2618960) in healthy subjects – a randomized, double‐blind, placebo‐controlled study

Cited by 38 publications

References 42 publications

Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke

Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke

Synergism between IL7R and CXCR4 drives BCR-ABL induced transformation in Philadelphia chromosome-positive acute lymphoblastic leukemia

Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia

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