Rationally designed approaches to augment CAR-T therapy for solid tumor treatment
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 d...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-03-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X23003511 |
| _version_ | 1797449802682728448 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chaojie Zhu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T14:30:18Z |
| format | Article |
| id | doaj.art-faea27ba51624a71a95eebd08b85090d |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-03-09T14:30:18Z |
| publishDate | 2024-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-faea27ba51624a71a95eebd08b85090d2023-11-28T04:06:16ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-03-0133377395Rationally designed approaches to augment CAR-T therapy for solid tumor treatmentChaojie Zhu0Qing Wu1Tao Sheng2Jiaqi Shi3Xinyuan Shen4Jicheng Yu5Yang Du6Jie Sun7Tingxizi Liang8Kaixin He9Yuan Ding10Hongjun Li11Zhen Gu12Weilin Wang13Key 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, ChinaLiangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China; Department of Cell Biology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, ChinaKey Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaKey Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaDepartment 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.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.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.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.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.http://www.sciencedirect.com/science/article/pii/S2452199X23003511CAR-T therapyCancer immunotherapyDrug deliveryCAR construct designTumor modulationDelivery strategy |
| spellingShingle | 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 Rationally designed approaches to augment CAR-T therapy for solid tumor treatment Bioactive Materials CAR-T therapy Cancer immunotherapy Drug delivery CAR construct design Tumor modulation Delivery strategy |
| title | Rationally designed approaches to augment CAR-T therapy for solid tumor treatment |
| title_full | Rationally designed approaches to augment CAR-T therapy for solid tumor treatment |
| title_fullStr | Rationally designed approaches to augment CAR-T therapy for solid tumor treatment |
| title_full_unstemmed | Rationally designed approaches to augment CAR-T therapy for solid tumor treatment |
| title_short | Rationally designed approaches to augment CAR-T therapy for solid tumor treatment |
| title_sort | rationally designed approaches to augment car t therapy for solid tumor treatment |
| topic | CAR-T therapy Cancer immunotherapy Drug delivery CAR construct design Tumor modulation Delivery strategy |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X23003511 |
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