Related Experiment Video

Updated: Jan 27, 2026

Minimally Invasive Isolated Limb Perfusion (MI-ILP) for Locally Advanced Melanomas and Sarcomas of the Extremity
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Minimally Invasive Isolated Limb Perfusion (MI-ILP) for Locally Advanced Melanomas and Sarcomas of the Extremity

Published on: January 31, 2025

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PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue

Henry G Smith1,2, David Mansfield1, Victoria Roulstone1

  • 1Targeted Therapy Team, The Institute of Cancer Research, London, United Kingdom.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 20, 2019
PubMed
Abstract

Insights

Combining oncolytic vaccinia virus (GLV-1h68) via isolated limb perfusion with PD-1 blockade shows promise for treating sarcoma. This novel approach enhances antitumor immunity and prevents relapse in preclinical models.

Area of Science:

  • Oncology
  • Immunotherapy
  • Virology

Background:

  • Metastatic sarcoma presents a significant unmet clinical need.
  • Immune checkpoint inhibitor monotherapy demonstrates limited efficacy in sarcoma.
  • Novel combination therapies are required to improve treatment outcomes.

Purpose of the Study:

  • To investigate the potential of oncolytic vaccinia virus (GLV-1h68) delivered via isolated limb perfusion (ILP) to enhance antitumor immune responses.
  • To evaluate the combination of viral ILP and PD-1 blockade for sarcoma treatment.
  • To assess the in vitro and in vivo efficacy of this combined approach.

Main Methods:

  • Utilized an established animal model of extremity sarcoma.
  • Administered locoregional delivery of GLV-1h68 via ILP, combined with biochemotherapy (melphalan/TNFα).
  • Performed in vitro assays to detect markers of immunogenic cell death in sarcoma cell lines.

Main Results:

  • PD-1 blockade monotherapy showed minimal efficacy, consistent with clinical observations.
  • Pretreatment with viral ILP significantly improved treatment responses.
  • The combination therapy prevented local and distant relapse, leading to cure in a refractory model.
  • Observed increased intratumoral CD8+ T cells and enhanced dendritic cell activation, indicating immune modulation.
  • GLV-1h68 induced immunogenic cell death markers in human sarcoma cell lines.

Conclusions:

  • Viral ILP combined with PD-1 blockade augments antitumor immune responses.
  • This combination transforms a locoregional therapy into a potentially effective systemic treatment for sarcoma.
  • The findings warrant further translational evaluation for clinical application.

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