1. Academic Validation
  2. Tumor microenvironment-modulating oncolytic adenovirus combined with GSK-3β inhibitor enhances antitumor immune response against bladder cancer

Tumor microenvironment-modulating oncolytic adenovirus combined with GSK-3β inhibitor enhances antitumor immune response against bladder cancer

  • Front Immunol. 2024 May 15:15:1360436. doi: 10.3389/fimmu.2024.1360436.
A-Rum Yoon 1 2 3 Ao Jiao 1 JinWoo Hong 4 Bomi Kim 1 Chae-Ok Yun 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea.
  • 2 Institute of Nano Science and Technology (INST), Hanyang University, Seoul, Republic of Korea.
  • 3 Hanyang Institute of Bioscience and Biotechnology (HY-IBB), Hanyang University, Seoul, Republic of Korea.
  • 4 GeneMedicine Co., Ltd., Seoul, Republic of Korea.
Abstract

Bladder Cancer is a common type of Cancer around the world, and the majority of patients are diagnosed with non-muscle-invasive bladder Cancer (NMIBC). Although low-risk NMIBC has a good prognosis, the disease recurrence rate and development of treatment-refractory disease remain high in intermediate- to high-risk NMIBC patients. To address these challenges for the treatment of NMIBC, a novel combination therapy composed of an oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and relaxin (RLX; HY-oAd) and a clinical-stage glycogen synthase kinase (GSK)-3β inhibitor (9-ING-41; elraglusib) was investigated in the present report. Our findings demonstrate that HY-oAd and 9-ING-41 combination therapy (HY-oAd+9-ING-41) exerted superior inhibition of tumor growth compared with respective monotherapy in a syngeneic NMIBC tumor model. HY-oAd+9-ING-41 induced high-level tumor extracellular matrix (ECM) degradation and a more potent antitumor immune response than the respective monotherapy. In detail, HY-oAd+9-ING-41 induced superior accumulation of intratumoral T cells, prevention of immune cell exhaustion, and induction of tumor-specific adaptive immune response compared to either monotherapy. Collectively, these results demonstrate that the combination of HY-oAd and 9-ING-41 may be a promising approach to elicit a potent antitumor immune response against bladder Cancer.

Keywords

GSK-3β inhibitor; adenovirus; antitumor immune response; bladder cancer; oncolytic virus.

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