4.7 Review

ENPP1 Immunobiology as a Therapeutic Target

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Human antibodies targeting ENPP1 as candidate therapeutics for cancers

Xiaojie Chu et al.

Summary: ENPP1, a type II transmembrane glycoprotein, is highly expressed in various cancers and associated with poor prognosis. In this study, two high-affinity and specific anti-ENPP1 Fab antibodies, 17 and 3G12, were isolated and characterized. Antibody-drug conjugates, IgG-based bispecific T-cell engagers, and CAR T-cells were generated based on these antibodies, all demonstrating potent killing of ENPP1-expressing cells. These antibody-derived modalities hold promise as therapeutic candidates for cancers expressing human ENPP1.

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Design, synthesis and biological evaluation studies of novel small molecule ENPP1 inhibitors for cancer immunotherapy

Mukesh Gangar et al.

Summary: ENPP1 is an attractive therapeutic target for cancer immunotherapy, acting as a critical phosphodiesterase that negatively regulates the STING pathway. Novel non-nucleotidic thioguanine based small molecule inhibitors of ENPP1 have shown promising in vitro potency and potent anti-tumor response in vivo, providing a good starting point for potentially effective cancer immunotherapy agents.

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Musculoskeletal Comorbidities and Quality of Life in ENPP1-Deficient Adults and the Response of Enthesopathy to Enzyme Replacement Therapy in Murine Models

Carlos R. Ferreira et al.

Summary: ENPP1 deficiency leads to various musculoskeletal complications impacting quality of life; Treatment with recombinant ENPP1 in mice shows partial suppression of enthesopathy; The study contributes to a better understanding of the pathophysiology of ENPP1 deficiency.

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Yujiro Kidani et al.

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Borja Ruiz-Fernandez de Cordoba et al.

Summary: Locoregional failure in breast cancer patients after surgery and irradiation is linked to a poor prognosis. The ENPP1/HP axis is exploited by tumor cells to promote local recurrence by suppressing immune cells. Blocking this axis offers new opportunities for therapeutic intervention.

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Roy S. Herbst et al.

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IL8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy

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Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis

Jun Li et al.

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High expression of ENPP1 in high-grade serous ovarian carcinoma predicts poor prognosis and as a molecular therapy target

Hanzhi Wang et al.

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