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Rationally designed approaches to augment CAR-T therapy for solid tumor treatment

Bioactive Materials 2024年第3期33卷 377-395页

作者： Chaojie Zhu Qing Wu Tao Sheng Jiaqi Shi Xinyuan Shen Jicheng Yu Yang Du Jie Sun Tingxizi Liang Kaixin He Yuan Ding Hongjun Li Zhen Gu Weilin Wang Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou311121China Department of Cell Biology School of MedicineZhejiang UniversityHangzhouZhejiang310058China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic tumor of Zhejiang Province HangzhouZhejiang310009China ZJU-Pujian Research&Development Center of Medical Artificial Intelligence for Hepatobiliary and Pancreatic Disease HangzhouZhejiang310058China Jinhua Institute of Zhejiang University Jinhu1321299China Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou310016China

Chimeric antigen receptor T cell denoted as CAR-T therapy has realized incredible therapeutic advancements for B cell malignancy ***,its therapeutic validity has yet to be successfully achieved in solid *** from hematological cancers,solid tumors are characterized by dysregulated blood vessels,dense extracellular matrix,and filled with immunosuppressive signals,which together result in CAR-T cells’insufficient infiltration and rapid *** insufficient recognition of tumor cells and tumor heterogeneity eventually causes cancer *** addition,CAR-T therapy also raises safety concerns,including potential cytokine release storm,on-target/off-tumor toxicities,and neuro-system side *** we comprehensively review various targeting aspects,including CAR-T cell design,tumor modulation,and delivery *** believe it is essential to rationally design a combinatory CAR-T therapy via constructing optimized CAR-T cells,directly manipulating tumor tissue microenvironments,and selecting the most suitable delivery strategy to achieve the optimal outcome in both safety and efficacy.

关键词： CAR-T therapy Cancer immunotherapy Drug delivery CAR construct design tumor modulation Delivery strategy

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Mesenchymal stromal cells' role in tumor microenvironment:involvement of signaling pathways

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Cancer Biology & Medicine 2017年第2期14卷 129-141页

作者： Armel Herve Nwabo Kamdje Paul Takam Kamga Richard Tagne Simo Lorella Vecchio Paul Faustin Seke Etet Jean Marc Muller Giulio Bassi Erique Lukong Raghuveera Kumar Goel Jeremie Mbo Amvene Mauro Krampera Department of Biomedical Sciences University of Ngaoundere Laboratory University of Verona Department of Basic Health SciencesCollege of Applied Medical SciencesQassim University Faculty of Science University of Poitiers Department of Biochemistry College of MedicineUniversity of Saskatchewan

Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like "wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed.

关键词： Mesenchymal stromal cells systemic circulation migration homing tumor modulation signaling pathways chemoresistance

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