Super natural killer cells that target metastases in the tumor draining lymph nodes

Biomaterials. 2016 Jan:77:66-76. doi: 10.1016/j.biomaterials.2015.11.001. Epub 2015 Nov 2.

Abstract

Tumor draining lymph nodes are the first site of metastasis in most types of cancer. The extent of metastasis in the lymph nodes is often used in staging cancer progression. We previously showed that nanoscale TRAIL liposomes conjugated to human natural killer cells enhance their endogenous therapeutic potential in killing cancer cells cultured in engineered lymph node microenvironments. In this work, it is shown that liposomes decorated with apoptosis-inducing ligand TRAIL and an antibody against a mouse natural killer cell marker are carried to the tumor draining inguinal lymph nodes and prevent the lymphatic spread of a subcutaneous tumor in mice. It is shown that targeting natural killer cells with TRAIL liposomes enhances their retention time within the tumor draining lymph nodes to induce apoptosis in cancer cells. It is concluded that this approach can be used to kill cancer cells within the tumor draining lymph nodes to prevent the lymphatic spread of cancer.

Keywords: Liposomes; Nanotechnology; Natural killer cells; TRAIL; Tumor-draining lymph nodes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Ly / immunology
  • Apoptosis / immunology
  • Cell Line, Tumor
  • Colonic Neoplasms / pathology
  • Cytotoxicity, Immunologic
  • Humans
  • Immunoconjugates / therapeutic use
  • Injections, Subcutaneous
  • Killer Cells, Natural / immunology*
  • Liposomes
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily B / immunology
  • Neoplasm Metastasis / immunology
  • Neoplasm Metastasis / therapy*
  • Recombinant Proteins / immunology
  • TNF-Related Apoptosis-Inducing Ligand / immunology
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antigens, Ly
  • Immunoconjugates
  • Klrb1c protein, mouse
  • Liposomes
  • NK Cell Lectin-Like Receptor Subfamily B
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human