Improved activation toward primary colorectal cancer cells by antigen-specific targeting autologous cytokine-induced killer cells

Clin Dev Immunol. 2012:2012:238924. doi: 10.1155/2012/238924. Epub 2012 Mar 19.

Abstract

Adoptive therapy of malignant diseases with cytokine-induced killer (CIK) cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR) with an antibody-defined specificity for carcinoembryonic antigen (CEA). CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA⁺ colon carcinoma cells, but less in presence of CEA⁻ cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / immunology
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Carcinoma / therapy
  • Cell Engineering
  • Colon / drug effects
  • Colon / immunology
  • Colon / pathology
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Cytokine-Induced Killer Cells / drug effects
  • Cytokine-Induced Killer Cells / immunology*
  • Cytokine-Induced Killer Cells / pathology
  • Cytokines / immunology
  • Cytokines / pharmacology
  • Cytotoxicity, Immunologic / drug effects*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Receptors, Antigen / genetics
  • Receptors, Antigen / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Tumor Cells, Cultured

Substances

  • CD28 Antigens
  • CD3 Complex
  • Carcinoembryonic Antigen
  • Cytokines
  • Receptors, Antigen