title: Improved activation toward primary colorectal cancer cells by antigen-specific targeting autologous cytokine-induced killer cells.
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.
authors.affiliation: Department of Neurosurgery, University of Bonn, 53127 Bonn, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schlimper
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Hombach
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
mesh_terms: D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D060846:Cell Engineering; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D055612:Cytokine-Induced Killer Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D011946:Receptors, Antigen