Adenoviral production of interleukin-2 at the tumor site removes the need for systemic postconditioning in adoptive cell therapy

Int J Cancer. 2017 Oct 1;141(7):1458-1468. doi: 10.1002/ijc.30839. Epub 2017 Jun 29.


Systemic high dose interleukin-2 (IL-2) postconditioning has long been utilized in boosting the efficacy of T cells in adoptive cell therapy (ACT) of solid tumors. The resulting severe off-target toxicity of these regimens renders local production at the tumor an attractive concept with possible safety gains. We evaluated the efficacy and safety of intratumorally administered IL-2-coding adenoviruses in combination with tumor-infiltrating lymphocyte therapy in syngeneic Syrian hamsters bearing HapT1 pancreatic tumors and with T cell receptor transgenic ACT in B16.OVA melanoma bearing C57BL/6 mice. The models are complementary: hamsters are semi-permissive for human oncolytic adenovirus, whereas detailed immunological analyses are possible in mice. In both models, local production of IL-2 successfully replaced the need for systemic recombinant IL-2 (rIL-2) administration and increased the efficacy of the cell therapy. Furthermore, vectored delivery of IL-2 significantly enhanced the infiltration of CD8+ T cells, M1-like macrophages, and B-cells while systemic rIL-2 increased CD25 + FoxP3+ T cells at the tumor. In contrast with vectored delivery, histopathological analysis of systemic rIL-2-treated animals revealed significant changes in lungs, livers, hearts, spleens, and kidneys. In summary, local IL-2 production results in efficacy and safety gains in the context of ACT. These preclinical assessments provide the rationale for ongoing clinical translation.

Keywords: T cell therapy; adoptive cell therapy; immunotherapy; interleukin-2; oncolytic adenovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology
  • Adenoviridae / metabolism*
  • Adoptive Transfer / methods
  • Animals
  • B-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Movement / immunology
  • Cricetinae
  • Disease Models, Animal
  • Female
  • Forkhead Transcription Factors / immunology
  • Genetic Vectors
  • Immunotherapy, Adoptive / methods*
  • Inflammation Mediators / blood
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / immunology
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lung / blood supply
  • Lung / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / transplantation
  • Macrophages / immunology
  • Male
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mesocricetus
  • Mice
  • Mice, Inbred C57BL
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / therapy*
  • Random Allocation
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Inflammation Mediators
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Recombinant Proteins