Immunotherapy for Tumor Metastasis by Artificial Antigen-Presenting Cells via Targeted Microenvironment Regulation and T-Cell Activation
| Autor: | Jieli Chen, Lihua Li, Xingyi Xu, Yao Lu, Chuanbin Mao, Jingwen Du, Xianfeng Yang, Changhai Ding |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lung Neoplasms
Materials science Surface Properties T cell medicine.medical_treatment Antigen-Presenting Cells CD8-Positive T-Lymphocytes Metastasis Mice Artificial antigen presenting cells Biomimetic Materials Cell Line Tumor Tumor Microenvironment medicine Animals Cytotoxic T cell General Materials Science Particle Size Melanoma Tumor microenvironment Cell Membrane Antibodies Monoclonal CD28 Oxides Immunotherapy medicine.disease medicine.anatomical_structure Manganese Compounds Cancer research Artificial Cells |
| Zdroj: | ACS Applied Materials & Interfaces. 13:55890-55901 |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|