A High-dose Pharmacokinetic Study of a New IgG4 Monoclonal Antibody Temelimab/GNbAC1 Antagonist of an Endogenous Retroviral Protein pHERV-W Env

Porchet, Hervé; Vidal, Virginie; Kornmann, Gabrielle; Malpass, Sam; Curtin, François

doi:10.1016/j.clinthera.2019.05.020

Cited by 11 publications

(6 citation statements)

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“…In preclinical studies, temelimab could rescue myelin basic protein (MBP) expression in OPCs and improve the symptoms caused by HERV-W env in an EAE mouse model [120,121,202]. Three clinical phase 1 studies in a total of 78 healthy male volunteers showed good tolerability of intravenous-administered temelimab at doses up to 110 mg/kg without severe adverse drug reactions [203][204][205]. A rather small study on 10 MS patients confirmed the doselinear pharmacokinetics and tolerability of previous studies [206,207].…”

Section: Possible Therapeutic Implicationsmentioning

confidence: 63%

Endogenous Retroviruses in Nervous System Disorders

et al. 2021

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Human endogenous retroviruses (HERV) have been implicated in the pathogenesis of several nervous system disorders including multiple sclerosis and amyotrophic lateral sclerosis. The toxicity of HERV-derived RNAs and proteins for neuronal cells has been demonstrated. The involvement of HERV in the pathogenesis of currently incurable diseases might offer new treatment strategies based on the inhibition of HERV activities by small molecules or therapeutic antibodies.

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Section: Possible Therapeutic Implicationsmentioning

confidence: 63%

Endogenous Retroviruses in Nervous System Disorders

et al. 2021

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“…Accordingly, the Institut Mérieux group, INSERM, and GeNeuro developed the MSRV-Env-targeting antibody GNbAC1 (now, Temelimab), which recently completed phase IIb clinical trials for the treatment of MS [ 1 ]. Clinical trials showed minimal side effects and good tolerance [ 378 ] as well as clinical improvements in patients with MS [ 1 ]. While Temelimab failed to show an effect on features of acute inflammation, it demonstrated preliminary radiological signs of possible anti-neurodegenerative effects for patients who had taken the highest dose [ 1 ].…”

Section: Discussion Of Novel Options For Cancer Treatment Facilitated...mentioning

confidence: 99%

HERVs and Cancer—A Comprehensive Review of the Relationship of Human Endogenous Retroviruses and Human Cancers

2023

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Genomic instability and genetic mutations can lead to exhibition of several cancer hallmarks in affected cells such as sustained proliferative signaling, evasion of growth suppression, activated invasion, deregulation of cellular energetics, and avoidance of immune destruction. Similar biological changes have been observed to be a result of pathogenic viruses and, in some cases, have been linked to virus-induced cancers. Human endogenous retroviruses (HERVs), once external pathogens, now occupy more than 8% of the human genome, representing the merge of genomic and external factors. In this review, we outline all reported effects of HERVs on cancer development and discuss the HERV targets most suitable for cancer treatments as well as ongoing clinical trials for HERV-targeting drugs. We reviewed all currently available reports of the effects of HERVs on human cancers including solid tumors, lymphomas, and leukemias. Our review highlights the central roles of HERV genes, such as gag, env, pol, np9, and rec in immune regulation, checkpoint blockade, cell differentiation, cell fusion, proliferation, metastasis, and cell transformation. In addition, we summarize the involvement of HERV long terminal repeat (LTR) regions in transcriptional regulation, creation of fusion proteins, expression of long non-coding RNAs (lncRNAs), and promotion of genome instability through recombination.

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“…It was important to establish safety in this specific patient population and the results obtained here are in line with the favorable temelimab safety profile obtained so far over the long term (up to twoyears) in multiple sclerosis patients 13 or at very high dose (up to 110 mg/kg). 15 This is probably due to the pHERV-W Env target antigen, which does not appear to play any physiological role, 9 and the absence of any known impact of temelimab on the immune system. This observation is reassuring and opens the way to further clinical trials with temelimab in particular in the pediatric population with early disease onset.…”

Section: Discussionmentioning

confidence: 99%