Scholarlink

Background <p>Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, with limited therapeutic options and inevitable recurrence despite maximal standard-of-care treatment. Photodynamic therapy (PDT) and oncolytic virotherapy have independently shown promise as alternative approaches, yet their combined potential in GBM remains incompletely explored.</p> Methods <p>We engineered a highly neuroattenuated herpes simplex virus type 1–based oncolytic virus (oHSV1), genetically related to talimogene laherparepvec (T-VEC), to express the photosensitizer KillerRed (KR) targeted to the cell plasma membrane (memKR). The cytolytic activity of this recombinant virus was evaluated in multiple human and murine GBM cell lines, patient-derived GBM cells, and three-dimensional (3D) spheroid models. We further assessed whether photoactivation of virus-encoded memKR or of the chemical photosensitizer phthalocyanine could enhance oHSV1-mediated cytotoxicity, including in spheroids infected via monocyte-based viral delivery.</p> Results <p>The recombinant memKR-encoding virus (oHSV1-KR) efficiently infected and killed GBM cells across 2D and 3D culture systems. Photoactivation of memKR significantly enhanced virus-mediated cytotoxicity in patient-derived GBM spheroids, particularly at lower viral doses. Similarly, phthalocyanine photoactivation augmented oHSV1-induced cell death, accelerating loss of viability in both monolayer cultures and spheroids. Monocyte-mediated delivery of oHSV1-KR resulted in effective viral transfer to GBM spheroids and retained responsiveness to photodynamic activation.</p> Conclusions <p>These findings demonstrate that combining oHSV1–based virotherapy with photodynamic activation enhances cytotoxic efficacy in advanced preclinical models of GBM. While limited to in vitro and ex vivo systems, this work establishes a modular and controllable therapeutic platform and provides a foundation for future in vivo and immunological studies aimed at translational development.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Antitumor activity of Oncolytic Herpes Symplex Virus Type 1 and photodynamic therapy in in vitro preclinical models of glioblastoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月27日

查看全文
  • Arianna Calistri,
  • Alessandra Rossetto,
  • Alberto Reale,
  • Maria Vittoria Fornaini,
  • Mariateresa Panarelli,
  • Luca Persano,
  • Elena Rampazzo,
  • Cristina Parolin,
  • Viola Donati,
  • Ana Gabriela de Oliveira do Rêgo,
  • Chiara Di Pietro,
  • Daniela Marazziti,
  • Fabio Mammano

摘要

Background

Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, with limited therapeutic options and inevitable recurrence despite maximal standard-of-care treatment. Photodynamic therapy (PDT) and oncolytic virotherapy have independently shown promise as alternative approaches, yet their combined potential in GBM remains incompletely explored.

Methods

We engineered a highly neuroattenuated herpes simplex virus type 1–based oncolytic virus (oHSV1), genetically related to talimogene laherparepvec (T-VEC), to express the photosensitizer KillerRed (KR) targeted to the cell plasma membrane (memKR). The cytolytic activity of this recombinant virus was evaluated in multiple human and murine GBM cell lines, patient-derived GBM cells, and three-dimensional (3D) spheroid models. We further assessed whether photoactivation of virus-encoded memKR or of the chemical photosensitizer phthalocyanine could enhance oHSV1-mediated cytotoxicity, including in spheroids infected via monocyte-based viral delivery.

Results

The recombinant memKR-encoding virus (oHSV1-KR) efficiently infected and killed GBM cells across 2D and 3D culture systems. Photoactivation of memKR significantly enhanced virus-mediated cytotoxicity in patient-derived GBM spheroids, particularly at lower viral doses. Similarly, phthalocyanine photoactivation augmented oHSV1-induced cell death, accelerating loss of viability in both monolayer cultures and spheroids. Monocyte-mediated delivery of oHSV1-KR resulted in effective viral transfer to GBM spheroids and retained responsiveness to photodynamic activation.

Conclusions

These findings demonstrate that combining oHSV1–based virotherapy with photodynamic activation enhances cytotoxic efficacy in advanced preclinical models of GBM. While limited to in vitro and ex vivo systems, this work establishes a modular and controllable therapeutic platform and provides a foundation for future in vivo and immunological studies aimed at translational development.