Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects

Abstract Immunotherapy has revolutionized the oncology treatment paradigm, and CAR-T cell therapy in particular represents a significant milestone in treating hematological malignancies. Nevertheless, tumor resistance due to target heterogeneity or mutation remains a Gordian knot for immunotherapy....

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Main Authors: Hongzhuo Qin, Zhaokai Zhou, Run Shi, Yumiao Mai, Yudi Xu, Fu Peng, Guangyang Cheng, Pengpeng Zhang, Wenjie Chen, Yun Chen, Yajun Chen, Ran Xu, Qiong Lu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Hematology & Oncology
Subjects:
Online Access:https://doi.org/10.1186/s13045-025-01701-6
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author Hongzhuo Qin
Zhaokai Zhou
Run Shi
Yumiao Mai
Yudi Xu
Fu Peng
Guangyang Cheng
Pengpeng Zhang
Wenjie Chen
Yun Chen
Yajun Chen
Ran Xu
Qiong Lu
author_facet Hongzhuo Qin
Zhaokai Zhou
Run Shi
Yumiao Mai
Yudi Xu
Fu Peng
Guangyang Cheng
Pengpeng Zhang
Wenjie Chen
Yun Chen
Yajun Chen
Ran Xu
Qiong Lu
author_sort Hongzhuo Qin
collection DOAJ
description Abstract Immunotherapy has revolutionized the oncology treatment paradigm, and CAR-T cell therapy in particular represents a significant milestone in treating hematological malignancies. Nevertheless, tumor resistance due to target heterogeneity or mutation remains a Gordian knot for immunotherapy. This review elucidates molecular mechanisms and therapeutic potential of next-generation immunotherapeutic tools spanning genetically engineered immune cells, multi-specific antibodies, and cell engagers, emphasizing multi-targeting strategies to enhance personalized immunotherapy efficacy. Development of logic gate modulation-based circuits, adapter-mediated CARs, multi-specific antibodies, and cell engagers could minimize adverse effects while recognizing tumor signals. Ultimately, we highlight gene delivery, gene editing, and other technologies facilitating tailored immunotherapy, and discuss the promising prospects of artificial intelligence in gene-edited immune cells.
format Article
id doaj-art-8c9601b5946f4c42b7939d55b0ecbda6
institution Kabale University
issn 1756-8722
language English
publishDate 2025-06-01
publisher BMC
record_format Article
series Journal of Hematology & Oncology
spelling doaj-art-8c9601b5946f4c42b7939d55b0ecbda62025-08-20T03:26:43ZengBMCJournal of Hematology & Oncology1756-87222025-06-0118116010.1186/s13045-025-01701-6Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospectsHongzhuo Qin0Zhaokai Zhou1Run Shi2Yumiao Mai3Yudi Xu4Fu Peng5Guangyang Cheng6Pengpeng Zhang7Wenjie Chen8Yun Chen9Yajun Chen10Ran Xu11Qiong Lu12Department of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, School of Pharmacy, Sichuan UniversityDepartment of Urology, First Affiliated Hospital of Zhengzhou UniversityDepartment of Lung Cancer, Tianjin Lung Cancer Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityDepartment of Urology, The Second Xiangya Hospital of Central South UniversityDepartment of Pharmacy, The Second Xiangya Hospital, Central South UniversityAbstract Immunotherapy has revolutionized the oncology treatment paradigm, and CAR-T cell therapy in particular represents a significant milestone in treating hematological malignancies. Nevertheless, tumor resistance due to target heterogeneity or mutation remains a Gordian knot for immunotherapy. This review elucidates molecular mechanisms and therapeutic potential of next-generation immunotherapeutic tools spanning genetically engineered immune cells, multi-specific antibodies, and cell engagers, emphasizing multi-targeting strategies to enhance personalized immunotherapy efficacy. Development of logic gate modulation-based circuits, adapter-mediated CARs, multi-specific antibodies, and cell engagers could minimize adverse effects while recognizing tumor signals. Ultimately, we highlight gene delivery, gene editing, and other technologies facilitating tailored immunotherapy, and discuss the promising prospects of artificial intelligence in gene-edited immune cells.https://doi.org/10.1186/s13045-025-01701-6Chimeric antigen receptorMulti-targetsLogic gateAdapter CARGene deliveryGene editing
spellingShingle Hongzhuo Qin
Zhaokai Zhou
Run Shi
Yumiao Mai
Yudi Xu
Fu Peng
Guangyang Cheng
Pengpeng Zhang
Wenjie Chen
Yun Chen
Yajun Chen
Ran Xu
Qiong Lu
Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects
Journal of Hematology & Oncology
Chimeric antigen receptor
Multi-targets
Logic gate
Adapter CAR
Gene delivery
Gene editing
title Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects
title_full Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects
title_fullStr Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects
title_full_unstemmed Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects
title_short Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects
title_sort insights into next generation immunotherapy designs and tools molecular mechanisms and therapeutic prospects
topic Chimeric antigen receptor
Multi-targets
Logic gate
Adapter CAR
Gene delivery
Gene editing
url https://doi.org/10.1186/s13045-025-01701-6
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