Biomaterial Database

Human Hyaluronidase PH20 Potentiates the Antitumor Activities of Mesothelin-Specific CAR-T Cells Against Gastric Cancer. 2021

Ruocong Zhao, and Yuanbin Cui, and Yongfang Zheng, and Shanglin Li, and Jiang Lv, and Qiting Wu, and Youguo Long, and Suna Wang, and Yao Yao, and Wei Wei, and Jie Yang, and Bin-Chao Wang, and Zhenfeng Zhang, and Hui Zeng, and Yangqiu Li, and Peng Li

Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.

T cell infiltration into tumors is essential for successful immunotherapy against solid tumors. Herein, we found that the expression of hyaluronic acid synthases (HAS) was negatively correlated with patient survival in multiple types of solid tumors including gastric cancer. HA impeded in vitro anti-tumor activities of anti-mesothelin (MSLN) chimeric antigen receptor T cells (CAR-T cells) against gastric cancer cells by restricting CAR-T cell mobility in vitro. We then constructed a secreted form of the human hyaluronidase PH20 (termed sPH20-IgG2) by replacing the PH20 signal peptide with a tPA signal peptide and attached with IgG2 Fc fragments. We found that overexpression of sPH20-IgG2 promoted CAR-T cell transmigration through an HA-containing matrix but did not affect the cytotoxicity or cytokine secretion of the CAR-T cells. In BGC823 and MKN28 gastric cancer cell xenografts, sPH20-IgG2 promoted anti-mesothelin CAR-T cell infiltration into tumors. Furthermore, mice infused with sPH20-IgG2 overexpressing anti-MSLN CAR-T cells had smaller tumors than mice injected with anti-MSLN CAR-T cells. Thus, we demonstrated that sPH20-IgG2 can enhance the antitumor activity of CAR-T cells against solid tumors by promoting CAR-T cell infiltration.

UI	MeSH Term	Description	Entries
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000076002	Hyaluronan Synthases	Membrane-associated glucuronosyltransferases that catalyze the reaction of UDP-N-acetyl-D-glucosamine and UDP-D-glucuronate to produce HYALURONAN. HYALURONAN SYNTHASE 2 (HAS2) is essential for embryogenesis and its expression by tumor cells is associated with metastasis.	HAS1 Protein,HAS2 Protein,HAS3 Protein,Hyaluronan Synthase,Hyaluronan Synthase 1,Hyaluronan Synthase 2,Hyaluronan Synthase 3,Hyaluronan Synthetase,Hyaluronate Synthase,Hyaluronate Synthetase,Hyaluronic Acid Synthetase,hasA Enzyme,3, Hyaluronan Synthase,Protein, HAS3,Synthase 1, Hyaluronan,Synthase 2, Hyaluronan,Synthase 3, Hyaluronan,Synthase, Hyaluronan,Synthase, Hyaluronate,Synthases, Hyaluronan,Synthetase, Hyaluronan,Synthetase, Hyaluronate,Synthetase, Hyaluronic Acid
D000076962	Receptors, Chimeric Antigen	Synthetic cellular receptors that reprogram T-LYMPHOCYTES to selectively bind antigens.	Chimeric Antigen Receptor,Chimeric T-Cell Receptor,Artificial T-Cell Receptors,Chimeric Antigen Receptors,Chimeric Immunoreceptors,Chimeric T-Cell Receptors,Antigen Receptor, Chimeric,Antigen Receptors, Chimeric,Artificial T Cell Receptors,Chimeric T Cell Receptor,Chimeric T Cell Receptors,Immunoreceptors, Chimeric,Receptor, Chimeric Antigen,Receptor, Chimeric T-Cell,Receptors, Artificial T-Cell,Receptors, Chimeric T-Cell,T-Cell Receptor, Chimeric,T-Cell Receptors, Artificial,T-Cell Receptors, Chimeric
D000090204	Mesothelin	An ANTIGEN present on the surface of certain types of normal cells and overexpressed in several human tumors, including OVARIAN CANCER.	CAK-1 Antigen,Megakaryocyte Potentiating Factor,Antigen, CAK-1,CAK 1 Antigen,Factor, Megakaryocyte Potentiating,Potentiating Factor, Megakaryocyte
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013047	Specific Pathogen-Free Organisms	Animals or humans raised in the absence of a particular disease-causing virus or other microorganism. Less frequently plants are cultivated pathogen-free.	Pathogen-Free Organisms,Specific Pathogen Free,Organism, Pathogen-Free,Organism, Specific Pathogen-Free,Organisms, Pathogen-Free,Organisms, Specific Pathogen-Free,Pathogen Free Organisms,Pathogen Free, Specific,Pathogen Frees, Specific,Pathogen-Free Organism,Pathogen-Free Organism, Specific,Pathogen-Free Organisms, Specific,Specific Pathogen Free Organisms,Specific Pathogen-Free Organism
D013274	Stomach Neoplasms	Tumors or cancer of the STOMACH.	Cancer of Stomach,Gastric Cancer,Gastric Neoplasms,Stomach Cancer,Cancer of the Stomach,Gastric Cancer, Familial Diffuse,Neoplasms, Gastric,Neoplasms, Stomach,Cancer, Gastric,Cancer, Stomach,Cancers, Gastric,Cancers, Stomach,Gastric Cancers,Gastric Neoplasm,Neoplasm, Gastric,Neoplasm, Stomach,Stomach Cancers,Stomach Neoplasm
D013601	T-Lymphocytes	Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.	T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D016019	Survival Analysis	A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.	Analysis, Survival,Analyses, Survival,Survival Analyses