title: TRUCKs: the fourth generation of CARs.
abstract: BACKGROUND
  Adoptive cell therapy of malignant diseases takes advantage of the cellular immune system to recognize and destroy cancer cells. This is impressively demonstrated by redirecting T cells with a chimeric antigen receptor (CAR) towards CD19, inducing complete and lasting remission of leukemia in more than two-thirds of patients in early phase trials.
  
  
  METHODS
  We outline how the CAR strategy is highly specific in redirecting T cells towards pre-defined target cells, however, reaches its limits when targeting solid tumors with a tremendous phenotypic heterogeneity. After initial tumor reduction by CAR T cells, antigen-negative cancer cells not recognized by CAR may give rise to tumor relapse. The situation may be overcome by CAR-mediated activation of T cells in the tumor, releasing inducible IL-12 which augments T-cell activation and attracts and activates innate immune cells to eliminate antigen-negative cancer cells in the targeted lesion.
  
  
  CONCLUSIONS
  CAR T cells with a transgenic 'payload', so-called TRUCK T cells or the 'fourth-generation' CAR T cells, are worthwhile to explore to shape the tumor environment by the inducible release of transgenic immune modifiers. Such TRUCK T cells are moreover envisioned to be applied in fields beyond cancer therapy including the therapy of virus infections, auto-immune diseases or metabolic disorders.
authors.affiliation: University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC), Clinic I for Internal Medicine , Robert-Koch-Street 21, D-50931 Cologne , Germany hinrich.abken@uk-koeln.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Chmielewski
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
mesh_terms: D000818:Animals; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D018664:Interleukin-12 / Q000276:immunology; D007938:Leukemia / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12
keywords: IL-12; T cell; adoptive cell therapy; chimeric antigen receptor; inducible cytokine; innate immunity