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

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

Bioactive Materials (Mar 2024)

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

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

Affiliations

Chaojie Zhu: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China
Qing Wu: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China
Tao Sheng: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China
Jiaqi Shi: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China
Xinyuan Shen: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China
Jicheng Yu: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
Yang Du: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
Jie Sun: Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China; Department of Cell Biology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China
Tingxizi Liang: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
Kaixin He: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
Yuan Ding: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang, 310009, China; ZJU-Pujian Research & Development Center of Medical Artificial Intelligence for Hepatobiliary and Pancreatic Disease, Hangzhou, Zhejiang, 310058, China; Corresponding author. Department of Hepatobiliary and Pancreatic Surgery the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
Hongjun Li: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China; Corresponding author. Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Zhen Gu: Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China; Jinhua Institute of Zhejiang University, Jinhua, 321299, China; Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China; Corresponding author. Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Weilin Wang: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang, 310009, China; ZJU-Pujian Research & Development Center of Medical Artificial Intelligence for Hepatobiliary and Pancreatic Disease, Hangzhou, Zhejiang, 310058, China; Corresponding author. Department of Hepatobiliary and Pancreatic Surgery the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.

Journal volume & issue: Vol. 33
pp. 377 – 395

Abstract

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Chimeric antigen receptor T cell denoted as CAR-T therapy has realized incredible therapeutic advancements for B cell malignancy treatment. However, its therapeutic validity has yet to be successfully achieved in solid tumors. Different 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 dysfunction. The insufficient recognition of tumor cells and tumor heterogeneity eventually causes cancer reoccurrences. In addition, CAR-T therapy also raises safety concerns, including potential cytokine release storm, on-target/off-tumor toxicities, and neuro-system side effects. Here we comprehensively review various targeting aspects, including CAR-T cell design, tumor modulation, and delivery strategy. We 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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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