journal article·2021-12-01

Immunotherapy for Tumor Metastasis by Artificial Antigen-Presenting Cells via Targeted Microenvironment Regulation and T-Cell Activation

Yao Lu, Lihua Li, Jingwen Du, Jieli Chen, Xingyi Xu, Xianfeng Yang, Changhai Ding, Chuanbin Mao

ACS Applied Materials & Interfaces· Volume 13· Issue 47
Publisher page

Abstract

Effective expansion of T-cells without ex vivo stimulation and maintenance of their antitumor functions in the complex tumor microenvironment (TME) are still daunting challenges in T-cell-based immunotherapy. Here, we developed biomimetic artificial antigen-presenting cells (aAPCs), ultrathin MnOx nanoparticles (NPs) functionalized with T-cell activators (anti-CD3/CD28 mAbs, CD), and tumor cell membranes (CMs) for enhanced lung metastasis immunotherapy. The aAPCs, termed CD-MnOx@CM, not only efficiently enhanced the expansion and activation of intratumoral CD8+ cytotoxic T-cells and dendritic cells after homing to homotypic metastatic tumors but also regulated the TME to facilitate T-cell survival through catalyzing the decomposition of intratumoral H2O2 into O2. Consequently, the aAPCs significantly inhibited the development of lung metastatic nodules and extended the survival of a B16–F10 melanoma metastasis model, while minimizing adverse events. Our work represents a new biomaterial strategy of inhibiting tumor metastasis through targeted TME regulation and in situ T-cell-based immunotherapy.
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Research context

OpenAlex topics: Nanoplatforms for cancer theranostics · Immunotherapy and Immune Responses · Immune cells in cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Clinical Research Center, Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China

Guangdong Key Lab of Orthopedic Technology and Implant, General Hospital of Southern Theater Command of PLA, Guangzhou, Guangdong 510010, China

The State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Fiber Laser Materials and Applied Techniques Guangdong Engineering Technology Research and Development Center of Special Optical Fiber Materials and Devices, School of Materials Science and Technology, South China University of Technology, Guangzhou, Guangdong 510640, China

Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, Australia

Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center, Institute for Biomedical Engineering, Science and Technology, University of Oklahoma, Norman, Oklahoma 73019, United States

School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China

Funding

China Postdoctoral Science Foundation · Southern Medical University · National Natural Science Foundation of China · Institute of Biomedical Engineering, Science and Technology, University of Oklahoma · China National Postdoctoral Program for Innovative Talents · Guangdong Basic and Applied Basic Research Foundation · President Foundation of Zhujiang Hospital

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