ASP7266, a Novel Antibody against Human Thymic Stromal Lymphopoietin Receptor for the Treatment of Allergic Diseases

Numazaki, Mako; Abe, Masaki; Hanaoka, Kaori; Imamura, Emiko; Maeda, Masashi; Kimura, Akihiko; Miyanohara, Jun; Saito, Tetsu; Arai, Kunizo; Suzuki, Hiroshi; Saita, Yuji

doi:10.1124/jpet.121.000686

Cited by 9 publications

(8 citation statements)

References 32 publications

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“…This approach may also reduce toxic side effects by not only specifically targeting JAK2, but also specific receptors and their complexes with JAK2. Another precision medicine approach for CRLF2/JAK2 -mutant ALL could also include strategies that inhibit TSLPR dimerization or activation ( Markovic and Savvides, 2020 ) potentially by using antagonistic monoclonal antibodies ( Zhang et al, 2011 ; Mohamed et al, 2021 ; Numazaki et al, 2021 ), inhibitors ( Van Rompaey et al, 2017 ), or CAR T-cells ( Qin et al, 2015 ). Therapeutic approaches that offer more selectivity for JAK2 should improve the toxic side effects associated with JAK2 inhibition.…”

Section: Discussion - Future Outlooksmentioning

confidence: 99%

JAK2 Alterations in Acute Lymphoblastic Leukemia: Molecular Insights for Superior Precision Medicine Strategies

Downes

McClure

McDougal

et al. 2022

Front. Cell Dev. Biol.

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Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, arising from immature lymphocytes that show uncontrolled proliferation and arrested differentiation. Genomic alterations affecting Janus kinase 2 (JAK2) correlate with some of the poorest outcomes within the Philadelphia-like subtype of ALL. Given the success of kinase inhibitors in the treatment of chronic myeloid leukemia, the discovery of activating JAK2 point mutations and JAK2 fusion genes in ALL, was a breakthrough for potential targeted therapies. However, the molecular mechanisms by which these alterations activate JAK2 and promote downstream signaling is poorly understood. Furthermore, as clinical data regarding the limitations of approved JAK inhibitors in myeloproliferative disorders matures, there is a growing awareness of the need for alternative precision medicine approaches for specific JAK2 lesions. This review focuses on the molecular mechanisms behind ALL-associated JAK2 mutations and JAK2 fusion genes, known and potential causes of JAK-inhibitor resistance, and how JAK2 alterations could be targeted using alternative and novel rationally designed therapies to guide precision medicine approaches for these high-risk subtypes of ALL.

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Section: Discussion - Future Outlooksmentioning

confidence: 99%

JAK2 Alterations in Acute Lymphoblastic Leukemia: Molecular Insights for Superior Precision Medicine Strategies

Downes

McClure

McDougal

et al. 2022

Front. Cell Dev. Biol.

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“…In a subset of patients with severe asthma, TSLP expression remains enhanced, independent of treatment with high-dose inhaled or oral corticosteroids [ 116 ]. Therefore, TSLP signalling blockade is a highly promising therapeutic approach for allergic diseases and asthma [ 117 , 118 , 119 ].…”

Section: Overview Of the Pharmacological Anti-tslp Strategiesmentioning

confidence: 99%

“…Humanized IgG1 monoclonal antibodies against TSLPR (RG7258, ASP7266) were also investigated in preclinical or phase I studies. Other approaches include TSLP cytokine traps, and small molecules targeting TSLP, such as baicalein [ 119 , 121 ]. Ecleralimab (CSJ117) is in undergoing development as an innovative dry powder inhaled anti-TSLP Fab antibody fragment that specifically targets the soluble TSLP, effectively preventing TSLP receptor activation [ 122 , 123 ].…”

Section: Overview Of the Pharmacological Anti-tslp Strategiesmentioning

confidence: 99%

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

Smolińska

Antolín‐Amérigo

Popescu

et al. 2023

IJMS

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Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as a critical player in the development and progression of allergy and asthma. It is primarily produced by epithelial cells and functions as a potent immune system activator. TSLP acts through interaction with its receptor complex, composed of the TSLP receptor (TSLPR) and interleukin-7 receptor alpha chain (IL-7Rα), activating downstream complex signalling pathways. The TSLP major isoform, known as long-form TSLP (lfTSLP), is upregulated in the airway epithelium of patients with allergic diseases. More research is warranted to explore the precise mechanisms by which short-form TSLP (sfTSLP) regulates immune responses. Understanding the dynamic interplay between TSLP and the dysfunctional epithelium provides insights into the mechanisms underlying allergy and asthma pathogenesis. Targeting TSLP represents an important therapeutic strategy, as it may upstream disrupt the inflammatory cascade and alleviate symptoms associated with allergic inflammation.

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“…Another antibody, ASP7266 (also known as UPB-101), is a fully human IgG1 monoclonal antibody that targets TSLPR 38 . In vitro studies have shown that ASP7266 can effectively inhibit TSLP-induced cell proliferation and CCL17 production, and TSLP-stimulated mDC-mediated naive CD4+ T-cell differentiation and IL-5 production by lineage-negative peripheral blood mononuclear cells.…”

Section: Targeting Tslp (Thymic Stromal Lymphopoietin) and Tslpr For ...mentioning

confidence: 99%

Role of the <i>TSLP</i> and its Receptor in the Treatment of Asthma

Estravís,

Dávila,

García-Sánchez

2023

BRN

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Thymic stromal lymphopoietin (TSLP) is a crucial cytokine in initiating and regulating immune responses. Various cell types, including epithelial cells, fibroblasts, and dendritic cells, synthesize TSLP. TSLP activates dendritic cells, which subsequently promote the differentiation of T cells into T-helper 2 (T H 2) cells, a subset of T cells that produce cytokines involved in allergic responses. Genetic studies have linked TSLP to the development of asthma and other inflammatory disorders, indicating its importance in the pathogenesis of these diseases. Inhibiting the TSLP-TSLR axis has been suggested as a precision medicine strategy for treating several phenotypes and endotypes of asthma. Tezepelumab is a human monoclonal antibody that selectively binds to TSLP, thereby blocking its interaction with its heterodimeric receptor, reducing inflammation in the airways, and improving asthma symptoms.

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ASP7266, a Novel Antibody against Human Thymic Stromal Lymphopoietin Receptor for the Treatment of Allergic Diseases

Cited by 9 publications

References 32 publications

JAK2 Alterations in Acute Lymphoblastic Leukemia: Molecular Insights for Superior Precision Medicine Strategies

JAK2 Alterations in Acute Lymphoblastic Leukemia: Molecular Insights for Superior Precision Medicine Strategies

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

Role of the <i>TSLP</i> and its Receptor in the Treatment of Asthma

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