Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells

Abstract

Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Based on the research of our group, we here introduce the new strategies being employed using nanoscale intelligent drug delivery systems to enhance the effects of cancer immunotherapy. We also provide a perspective on the further possible application of nanoparticles in more effective antitumor immunotherapy.

Keywords: cancer immunotherapy; dendritic cells; immune checkpoint inhibitors; nanoparticles; natural killer cells; tumor microenvironment; tumor vaccine.

Fig. 1. NLG919@DEAP-DPPA-1 nanoparticles for cancer immunotherapy.

a The antitumor mechanism of the multifunctional peptide in the tumor microenvironment. b Transmission electron microscopy images of nanoparticles under different pH conditions with or without recombinant human MMP-2 (rhMMP-2). Scale bars: 100 nm. c Treatment efficacy of peptide nanoparticles and the quantity of CD8⁺  T cells measured in melanoma-bearing mice. Copyright (2018), American Chemical Society.

Fig. 2. pH (low) insertion peptide (pHLIP)-Fc enhanced immunotherapy with natural killer cells.

a Mechanism by which pHLIP-Fc or pHLIP-mAb activates ADCC. b Comparison of pHLIPs at physiological pH and a weakly acidic pH. Scale bar: 50 µm. c Measurement of CRTAM-positive cells as activated NK cells and the inhibition of tumor growth. Fc/a: Fc fragments from mouse IgG2a; Fc/b: Fc fragments from a mouse. Copyright (2018) John Wiley & Sons, Inc.

Fig. 3. Biologically derived nanoparticles for activation of dendritic cells (DCs).

a Exosome-based dual vaccine. Tumor-derived exosomes were incubated with DCs to generate DC-derived membrane vesicles (DC-mvs), which were injected into mice. Copyright (2012) Elsevier Ltd. b Membrane-based tumor vaccine. The tumor cell membrane (antigen) and CpG (adjuvant) were codelivered to antigen-presenting cells (blue), and activated T cells (tan) killed tumor cells. Copyright (2017) John Wiley & Sons, Inc.