Cyto-Immuno-Therapy for Cancer: A Pathway Elicited by Tumor-Targeted, Cytotoxic Drug-Packaged Bacterially Derived Nanocells

Cancer Cell. 2020 Mar 16;37(3):354-370.e7. doi: 10.1016/j.ccell.2020.02.001.

Abstract

Immunotherapy has emerged as a powerful new chapter in the fight against cancer. However, it has yet to reach its full potential due in part to the complexity of the cancer immune response. We demonstrate that tumor-targeting EDV nanocells function as an immunotherapeutic by delivering a cytotoxin in conjunction with activation of the immune system. These nanocells polarize M1 macrophages and activate NK cells concurrently producing a Th1 cytokine response resulting in potent antitumor function. Dendritic cell maturation and antigen presentation follows, which generates tumor-specific CD8+ T cells, conferring prolonged tumor remission. The combination of cytotoxin delivery and activation of innate and adaptive antitumor immune responses results in a potent cyto-immunotherapeutic with potential in clinical oncology.

Keywords: PNU-159682; cancer; combined therapeutic; cyto-immunotherapy; immunotherapy; nanocell; supercytotoxin; tumor targeting.

Publication types

  • Case Reports
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Cell Line
  • Dendritic Cells / drug effects
  • Dendritic Cells / physiology
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Delivery Systems / methods*
  • ErbB Receptors / administration & dosage
  • ErbB Receptors / metabolism
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / pathology
  • Humans
  • Immunity, Innate / drug effects*
  • Immunotherapy / methods
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanostructures / chemistry
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / pathology
  • Salmonella typhimurium / cytology*

Substances

  • 3'-deamino-3'',4'-anhydro-(2''-methoxy-3''-oxy-4''-morpholinyl)doxorubicin
  • Antineoplastic Agents
  • Doxorubicin
  • EGFR protein, human
  • ErbB Receptors