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

Nanomedicine. 2022 Sep:45:102591. doi: 10.1016/j.nano.2022.102591. Epub 2022 Jul 27.

Abstract

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy
  • Immune Checkpoint Inhibitors
  • Immunotherapy, Adoptive
  • Mice
  • Nanogels
  • Neoplasms* / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen*
  • Tumor Microenvironment

Substances

  • Immune Checkpoint Inhibitors
  • Nanogels
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen