Cell membrane-anchored and tumor-targeted IL-12 T-cell therapy destroys cancer-associated fibroblasts and disrupts extracellular matrix in heterogenous osteosarcoma xenograft models

• Published in: Journal for immunotherapy of cancer Vol. 12; no. 1; p. e006991
• Main Authors: Hu, Jiemiao, Lazar, Alexander J, Ingram, Davis, Wang, Wei-Lien, Zhang, Wendong, Jia, Zhiliang, Ragoonanan, Dristhi, Wang, Jian, Xia, Xueqing, Mahadeo, Kris, Gorlick, Richard, Li, Shulin
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 09.01.2024; BMJ Publishing Group
• Series: Original research
• Subjects: Animals; Bone Neoplasms - therapy; Cancer-Associated Fibroblasts; Cell Membrane; Cell- and Tissue-Based Therapy; Clinical/Translational Cancer Immunotherapy; Cytokines; Disease Models, Animal; Extracellular Matrix; Heterografts; Humans; Immunotherapy, Adoptive; Interleukin-12; Lymphocytes, Tumor-Infiltrating; Osteosarcoma - therapy; Pediatrics; Tumor Microenvironment; Tumor Microenvironment; Pediatrics; Lymphocytes, Tumor-Infiltrating; Cytokines; Immunotherapy, Adoptive

BackgroundThe extracellular matrix (ECM) and cancer-associated fibroblasts (CAFs) play major roles in tumor progression, metastasis, and the poor response of many solid tumors to immunotherapy. CAF-targeted chimeric antigen receptor-T cell therapy cannot infiltrate ECM-rich tumors such as osteosarco...