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<p>HIV persistence in reservoirs despite antiretroviral therapy (ART) is a barrier to a permanent cure. We present the affinity-enhanced TCR bispecific IMC-M113V as a potential therapeutic for targeted HIV reservoir elimination. Preclinical studies demonstrate that IMC-M113V redirects T cells towards cells expressing the variable viral peptide, Gag<sub>77-85,</sub> presented by HLA-A*02:01 at low copy number, without binding to HIV-negative cells. Here, we conduct a first-in-human, open-label single ascending dose study of IMC-M113V (1.6-15 µg) in twelve HLA-A*02:01-positive males living with HIV on suppressive ART (EudraCT number 2021-002008-11). Participants receive one intravenous infusion of IMC-M113V on Day 1 and are monitored through Day 29 to evaluate safety, tolerability (primary endpoints) and pharmacodynamic (PD) activity (secondary endpoint). IMC-M113V is well tolerated and not associated with any serious adverse event. PD activity is dose-dependent and strongest in participants with highly IMC-M113V-sensitive Gag<sub>77-85</sub> variant sequences. Thus, we provide a promising foundation to evaluate multiple and higher doses of IMC-M113V as a strategy for achieving ART-free virological control.</p>

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Safety and biologic activity of a bispecific T cell receptor targeting HIV Gag in males living with HIV: a first-in-human trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月31日

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  • Linos Vandekerckhove,
  • Julie Fox,
  • Borja Mora-Peris,
  • Jordi Navarro,
  • Sabine D. Allard,
  • Alison J. Uriel,
  • Santiago Moreno Guillén,
  • Marta Boffito,
  • Frank A. Post,
  • Vicente Estrada,
  • Beatriz Mothe,
  • Mareva Delporte,
  • Adel Benlahrech,
  • Haseeb Rahman,
  • James Clubley,
  • Agatha Treveil,
  • Jonathan Chamberlain,
  • Rory Harrison,
  • Miriam Hock,
  • Yuan Yuan,
  • Jason Wustner,
  • Sylvie Moureau,
  • Andrew D. Whale,
  • Zoë Wallace,
  • Praveen K. Singh,
  • Kehmia Titanji,
  • Lucy Dorrell,
  • Sarah Fidler

摘要

HIV persistence in reservoirs despite antiretroviral therapy (ART) is a barrier to a permanent cure. We present the affinity-enhanced TCR bispecific IMC-M113V as a potential therapeutic for targeted HIV reservoir elimination. Preclinical studies demonstrate that IMC-M113V redirects T cells towards cells expressing the variable viral peptide, Gag77-85, presented by HLA-A*02:01 at low copy number, without binding to HIV-negative cells. Here, we conduct a first-in-human, open-label single ascending dose study of IMC-M113V (1.6-15 µg) in twelve HLA-A*02:01-positive males living with HIV on suppressive ART (EudraCT number 2021-002008-11). Participants receive one intravenous infusion of IMC-M113V on Day 1 and are monitored through Day 29 to evaluate safety, tolerability (primary endpoints) and pharmacodynamic (PD) activity (secondary endpoint). IMC-M113V is well tolerated and not associated with any serious adverse event. PD activity is dose-dependent and strongest in participants with highly IMC-M113V-sensitive Gag77-85 variant sequences. Thus, we provide a promising foundation to evaluate multiple and higher doses of IMC-M113V as a strategy for achieving ART-free virological control.