期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 45, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2022.102591
关键词
Adoptive cell therapy; Immune checkpoint blockade; Cell backpack; Tumor microenvironment; CAR-T therapy
资金
- National Natural Science Foundation of China [82150410455]
- Natural Sci-ence Foundation of Jiangsu Province [BK20200861]
- Suzhou Science and Technology Development Project [ZXL2019246]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
In this study, we demonstrate an innovative approach to enhance the treatment outcome of Adoptive Cell Therapy (ACT) for solid tumors by safely anchoring immune checkpoint inhibitors onto T cell surface using bio-orthogonal click chemistry.
The efficacy of Adoptive Cell Therapy (ACT) for solid tumor is still mediocre. This is mainly because tumor cells can hijack ACT T cells' immune checkpoint pathways to exert immunosuppression in the tumor microenvironment. Immune Checkpoint Inhibitors such as anti-PD-1 (aPD1) can counter the immunosuppression, but the synergizing effects of aPD1 to ACT was still not satisfactory. Here we demonstrate an approach to safely anchor aPD1-formed nanogels onto T cell surface via bio-orthogonal click chemistry before adoptive transfer. The spatial -temporal co-existence of aPD1 with ACT T cells and the responsive drug release significantly improved the treatment outcome of ACT in murine solid tumor model. The average tumor weight of the group treated by cell-surface anchored aPD1 was only 18 % of the group treated by equivalent dose of free aPD1 and T cells. The technology can be broadly applicable in ACTs employing natural or Chimeric Antigen Receptor (CAR) T cells.(c) 2022 Elsevier Inc. All rights reserved.
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