Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma

Immunol Rev. 2014 Jan;257(1):83-90. doi: 10.1111/imr.12125.


Adoptive T-cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo-engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody-derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR, considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T-cell therapy by modulating the tumor stroma by a CAR T-cell-secreted transgenic cytokine like interleukin-12 (IL-12). The basic process is that CAR T cells, when activated by their CAR, deposit IL-12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected for universal cytokine-mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials.

Keywords: IL-12; T cell; adoptive cell therapy; chimeric antigen receptor; inducible cytokine; innate immunity; stroma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Humans
  • Immunity, Innate
  • Immunologic Factors / genetics
  • Immunologic Factors / metabolism
  • Immunomodulation
  • Immunotherapy, Adoptive
  • Interleukin-12 / metabolism
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / metabolism*
  • Recombinant Fusion Proteins*
  • Stromal Cells / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*


  • Cytokines
  • Immunologic Factors
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Interleukin-12