Expandable Immunotherapeutic Nanoplatforms Engineered from Cytomembranes of Hybrid Cells Derived from Cancer and Dendritic Cells

Adv Mater. 2019 May;31(18):e1900499. doi: 10.1002/adma.201900499. Epub 2019 Mar 25.

Abstract

Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co-stimulatory molecules for robust immunotherapy. FMs share the tumor's self-targeting character with the parent cancer cells. In bilateral tumor-bearing mouse models, the FM-coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post-nanophotosensitizer-induced photodynamic therapy (PDT). The FM-induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy-caused regression of the irradiation-free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor-specific immunotherapy-based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.

Keywords: fused cells; homotypic targeting; hybrid cytomembrane; immunotheraputic platform; photodynamic therapy.

MeSH terms

  • Animals
  • Antibodies / chemistry
  • Antibodies / immunology
  • Cell Line, Tumor
  • Cell Membrane / chemistry*
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Hyaluronan Receptors / immunology
  • Immunotherapy*
  • Metal-Organic Frameworks / chemistry
  • Mice
  • Mice, Nude
  • Nanostructures / chemistry*
  • Nanostructures / therapeutic use
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Photochemotherapy
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / therapeutic use
  • Porphyrins / chemistry
  • Porphyrins / therapeutic use
  • Transplantation, Heterologous
  • Zirconium / chemistry

Substances

  • Antibodies
  • Histocompatibility Antigens Class II
  • Hyaluronan Receptors
  • Metal-Organic Frameworks
  • Photosensitizing Agents
  • Porphyrins
  • Zirconium