2. Academic Validation
  3. Preclinical and clinical evaluation of intratumoral injection of an IL-12 expressing SKV-012 oncolytic virus for advanced solid tumors

Preclinical and clinical evaluation of intratumoral injection of an IL-12 expressing SKV-012 oncolytic virus for advanced solid tumors

  • J Immunother Cancer. 2025 Jun 8;13(6):e011642. doi: 10.1136/jitc-2025-011642.
Zheng Jiang # 1,  Nian Yang # 2,  Jing Jin # 1,  Zongliang Zhang 2,  Huaqing Lu 2,  Long Xu 2,  Yongdong Chen 2,  Liyuan Jin 3,  Liangxue Zhou 3 4 5,  Hui Yang 6,  Jun Liu 6,  Weiwei Zhang 7,  Aiping Tong 8 9 10,  Xingchen Peng 11
Affiliations

Affiliations

  • 1 Department of Biotherapy, Cancer Center, Sichuan University West China Hospital, Chengdu, Sichuan, China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
  • 3 Fifth People's Hospital of Ningxia Hui Autonomous Region, Shizuishan, Ningxia, China.
  • 4 Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
  • 5 Department of Neurosurgery, NHC Key Laboratory of Nuclear Technology Medical Transformation（Mianyang Central Hospital), School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, China.
  • 6 Department of Otolaryngology- Head & Neck Surgery, West China Hospital of Sichuan University, Chengdu, China.
  • 7 Cancer Prevention and Treatment Institute of Chengdu, Department of Oncology, Chengdu Fifth People's Hospital (The Second Clinical Medical College,Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, China.
  • 8 State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China pxx2014@163.com aipingtong@scu.edu.cn.
  • 9 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Medicine, Chengdu, China.
  • 10 Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan, China.
  • 11 Department of Biotherapy, Cancer Center, Sichuan University West China Hospital, Chengdu, Sichuan, China pxx2014@163.com aipingtong@scu.edu.cn.
  • # Contributed equally.
PMID: 40484644 DOI: 10.1136/jitc-2025-011642
Abstract

Background: SKV-012 is a novel engineered oncolytic virus (containing the viral neurovirulence ICP34.5 gene transcribed by the Survivin promoter with an upstream genetic component of interleukin-12 (IL-12) driven by the cytomegalovirus promoter) that preferentially replicates in tumors and helps stimulate antitumor immune responses.

Methods: We evaluated SKV-012's safety and efficacy in preclinical models. In a phase I trial, patients with advanced solid tumors received intratumoral injections of escalating doses of SKV-012. Primary endpoints were safety and tolerability, while secondary endpoints were antitumor response and changes in the tumor microenvironment (TME), assessed by RECIST v1.1 criteria and multiplex immunohistochemistry and single-cell transcriptome analysis.

Results: SKV-012-infected tumor cells secreted high levels of IL-12 and exhibited increased ICP34.5 expression. The combination of oncolytic herpesvirus and IL-12 was proven to reshape the TME by increasing the infiltration of immune cells, thereby significantly inducing immune cell-mediated cytolysis of tumor cells both in vitro and in animal models. Based on this, we then tested the safety, efficacy and immunogenicity of SKV-012 in patients with advanced solid cancers in a phase I clinical trial (NCT06080984). No dose-limiting toxicities were observed, and adverse events were mild. Three patients achieved partial responses; one had stable disease and two had progressive disease. SKV-012 altered the TME, increasing CD8+ T cells, conventional dendritic cells, and programmed death-ligand 1 expression.

Conclusions: Intratumoral SKV-012 injections demonstrated a favorable safety profile and promising efficacy in animal models and patients with advanced cancers, thereby implicating its potential for clinical application in treatment-resistant advanced solid tumors.

Keywords

Head and Neck Cancer; Melanoma; Oncolytic virus; Sarcoma.

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