Cancer cell membrane-wrapped nanoparticles for cancer immunotherapy: A review of current developments

Abstract

Background: As the forefront of nanomedicine, bionic nanotechnology has been widely used for drug delivery in order to obtain better efficacy but less toxicity for cancer treatments. With the rise of immunotherapy, the combination of nanotechnology and immunotherapy will play a greater potential of anti-tumor therapy. Due to its advantage of homologous targeting and antigen library from source cells, cancer cell membrane (CCM)-wrapped nanoparticles (CCNPs) has become an emerging topic in the field of immunotherapy.

Key scientific concepts of review: CCNP strategies include targeting or modulating the tumor immune microenvironment and combination therapy with immune checkpoint inhibitors and cancer vaccines. This review summarizes the current developments in CCNPs for cancer immunotherapy and provides insight into the challenges of transferring this technology from the laboratory to the clinic as well as the potential future of this technology.

Conclusion: This review described CCNPs have enormous potential in cancer immunotherapy, but there are still challenges in terms of translating their effects in vitro to the clinical setting. We believe that these challenges can be addressed in the future with a focus on individualized treatment with CCNPs as well as CCNPs combined with other effective treatments.

Keywords: cancer cell membrane; drug delivery; immunotherapy; membrane-wrapped; nanoparticle; nanovaccine.

Figure 1

Application of cancer cell membrane-wrapped nanoparticles for cancer immunotherapy. (A) The structure of CCNPs; (B) Mechanism of CCNPs targeting on TME: CCNPs directly carry TSAs from cancer cell membranes or by different stimuli, such as PTT, then release TAAs. The released TSAs/TAAs, together with the immune adjuvant (R837/Liposome), drive the maturation of DCs. The CCNPs also used the tumor-specific enzyme metallomatrix protease 2 (MMP2) to dramatically extend the half-life of the peptides, e.g. PD-L1 inhibitory peptides, or combined with PD-1/PD-L1 inhibitors to further enhance the anti-tumor effect. The above processes promote the infiltration of CTLs for treating distant metastasis. (C) Combination therapy based on ICIs: A combination therapeutic strategy that includes PDT, PTT and SDT, particularly robust anti-cancer agents loaded on CCNPs, results in enhanced anti-tumor effect of PD-1/PD-L1 inhibitors. (D) Cancer vaccines: As tumor vaccines, CCNPs can directly release TSAs/TAAs, release cytokines to promote the transformation of functional immune cells or are added special molecules on the cancer cell membrane to increase the antigen presentation to DCs, thus further enhancing the anti-tumor immune effect. Abbreviations: CCNPs = cancer cell membrane-wrapped nanoparticles, TIME = tumor immune microenvironment, TAAs = tumor-associated antigens, TSAs = tumor-specific antigens, PTT = photothermal therapy, PDT = photodynamic therapy, MMP2 = metallomatrix protease 2, PD-L1/PD-1 = programmed death-ligand 1/programmed death-1, CTLs = cytotoxic T lymphocytes, DCs = dendritic cells, ICIs = immune checkpoint inhibitors, NPs = nanoparticles, SDT = sonodynamic therapy, PDT = photodynamic therapy, Th1 cell = T helper 1 cell, CBP-12 = 12-mer Clec9a binding peptide.