4.6 Article

Enhancing adoptive T cell therapy for solid tumor with cell-surface anchored immune checkpoint inhibitor nanogels

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Publisher

ELSEVIER
DOI: 10.1016/j.nano.2022.102591

Keywords

Adoptive cell therapy; Immune checkpoint blockade; Cell backpack; Tumor microenvironment; CAR-T therapy

Funding

  1. National Natural Science Foundation of China [82150410455]
  2. Natural Sci-ence Foundation of Jiangsu Province [BK20200861]
  3. Suzhou Science and Technology Development Project [ZXL2019246]
  4. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)

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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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