Nectin-4: a Tumor Cell Target and Status of Inhibitor Development

Bouleftour, Wafa; Sargos, P.; Magné, Nicolas

doi:10.1007/s11912-023-01360-1

Cited by 6 publications

(5 citation statements)

References 49 publications

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“… 138 Nectin‐4, EGFR, Trop‐2, tissue factor, CD19, and folate receptor‐a have been added to the repository of druggable targets and recent approvals (Table 4 ), further supporting the development of therapies targeting these molecules. 139 , 140 , 141 Ocular toxicity including changes in corneal epithelium and conjunctiva leading to vision changes, severe loss of vision and corneal ulceration were listed as significant adverse events reported in the FDA boxed warning for BCMA‐targeting belantamab mafodotin, Blenrep (approved in 2020 for specific cases of relapsed or refractory multiple myeloma) was withdrawn in late 2023. 142 Proposed mechanisms contributing to the ocular toxicity include premature payload release due to extracellular cleavage of linker, subsequent intracellular metabolism of linker‐cytotoxic payload and cellular uptake mediated by Fc‐receptors.…”

Section: Ab‐drug‐conjugatesmentioning

confidence: 99%

“…Stem cell‐like breast cancer cells are additionally shown to be targeted by T‐DM1, contributing to clinical efficacy 138 . Nectin‐4, EGFR, Trop‐2, tissue factor, CD19, and folate receptor‐a have been added to the repository of druggable targets and recent approvals (Table 4), further supporting the development of therapies targeting these molecules 139–141 . Ocular toxicity including changes in corneal epithelium and conjunctiva leading to vision changes, severe loss of vision and corneal ulceration were listed as significant adverse events reported in the FDA boxed warning for BCMA‐targeting belantamab mafodotin, Blenrep (approved in 2020 for specific cases of relapsed or refractory multiple myeloma) was withdrawn in late 2023 142 .…”

Section: Ab‐drug‐conjugatesmentioning

confidence: 99%

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Immune‐related adverse events of antibody‐based biological medicines in cancer therapy

Rajagopal,

MacLeod,

Corogeanu

et al. 2024

J Cellular Molecular Medi

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Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of rituximab as the first monoclonal antibody (mAb) for cancer treatment, several mAbs and antibody (Ab)‐based therapies have been approved for the treatment of solid tumour malignancies and other cancers. These Abs function by either blocking oncogenic pathways or angiogenesis, modulating immune response, or by delivering a conjugated drug. The use of Ab‐based therapy in cancer patients who could benefit from the treatment, however, is still limited by associated toxicity profiles which may stem from biological features and processes related to target binding, alongside biochemical and/or biophysical characteristics of the therapeutic Ab. A significant immune‐related adverse event (irAE) associated with Ab‐based therapies is cytokine release syndrome (CRS), characterized by the development of fever, rash and even marked, life‐threatening hypotension, and acute inflammation with secondary to systemic uncontrolled increase in a range of pro‐inflammatory cytokines. Here, we review irAEs associated with specific classes of approved, Ab‐based novel cancer immunotherapeutics, namely immune checkpoint (IC)‐targeting Abs, bispecific Abs (BsAbs) and Ab‐drug‐conjugates (ADCs), highlighting the significance of harmonization in preclinical assay development for safety assessment of Ab‐based biotherapeutics as an approach to support and refine clinical translation.

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Section: Ab‐drug‐conjugatesmentioning

confidence: 99%

Section: Ab‐drug‐conjugatesmentioning

confidence: 99%

Immune‐related adverse events of antibody‐based biological medicines in cancer therapy

Rajagopal,

MacLeod,

Corogeanu

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

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“…Based on the ASCENT study, the EVER-132-001 bridging study also showed that SG has good efficacy and safety in Chinese TNBC patients. 8 Based on the results of China bridging trial (EV-203, NCT04995419), enfortumab vedotin (EV, Padcev ® ) targeting Nectin-4 can be used as a platinumfree therapy for patients with locally advanced or metastatic urothelial cancer previously treated with PD-1/L1 inhibitors and platinum-based chemotherapy. The marketing authorization application for the biological product was accepted in China.…”

Section: Perspectivementioning

confidence: 99%

A new perspective in the research of antibody drug conjugate

Li¹,

Jiang²,

Xu³

2023

TIME

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<p>Antibody drug conjugate (ADC) combines the high specificity of monoclonal antibodies and the high activity of small molecule cytotoxic drugs through linkers to improve the targeting of tumor drugs and reduce the toxic side effects. Due to the advantages of clear targets, mature technology, and good selectivity, ADCs have shown excellent application prospects in hematological and solid tumor therapeutic fields. In this perspective, the selection of ADC-targeting antigens is described in the group of driver gene target antigens and non-driver gene target antigens to make more evident the importance of targeting antigens in advancing ADCs for tumor therapy. In the future, continued research and innovation in this field will help provide more effective, targeted, and personalized treatments for cancer patients, ultimately improving patients�� outcomes and quality of life.</p>

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“…Nectin-4 is a type I transmembrane polypeptide of adhesion molecules [21]. It has also been identified as a homolog of the poliovirus receptor (CD155/PVR) or poliovirus receptor-related (PRR) protein [30]. It plays an important role in the initiation and maintenance of adhesion connections in polarized epithelial cells [31].…”

Section: Nectin-4 and Cancersmentioning

confidence: 99%

Nectin-3 and Nectin-4: potential prognostic biomarkers for therapeutic targeting of cancer

Yang,

Ge,

Yang

et al. 2023

Trop. J. Pharm Res

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Nectin-3 and nectin-4 belong to the immunoglobulin (Ig) superfamily, and are Ca2+ -independent homophilic cell adhesion molecules. Nectin-3 is ubiquitous in adult tissues, and it enhances normal levels of synaptic formation. In contrast, nectin-4 is weakly-to-moderately expressed in normal human tissues. In recent years, studies have shown that nectin-3 is highly expressed in the nervous system. Moreover, it is associated with poor prognostic factors in distant metastases and malignant tumors with high vascular invasion such as pancreatic, lung and breast cancers. In particular, nectin-4 is overexpressed in various malignant tumors, and it is associated with proliferation, angiogenesis, metastasis, drug resistance, tumor relapse, DNA repair, cancer stemness, and poor prognosis. Unlike nectin-3, nectin-4 has become a potential prognostic biomarker and specific therapeutic target for cancer as there is no consensus on the significance of abnormal expression of nectin-3 in various cancers.

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Nectin-4: a Tumor Cell Target and Status of Inhibitor Development

Cited by 6 publications

References 49 publications

Immune‐related adverse events of antibody‐based biological medicines in cancer therapy

Immune‐related adverse events of antibody‐based biological medicines in cancer therapy

A new perspective in the research of antibody drug conjugate

Nectin-3 and Nectin-4: potential prognostic biomarkers for therapeutic targeting of cancer

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