Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors

Cancer Res. 2014 Sep 15;74(18):5195-205. doi: 10.1158/0008-5472.CAN-14-0697. Epub 2014 Jul 24.


The clinical efficacy of chimeric antigen receptor (CAR)-redirected T cells remains marginal in solid tumors compared with leukemias. Failures have been attributed to insufficient T-cell migration and to the highly immunosuppressive milieu of solid tumors. To overcome these obstacles, we have combined CAR-T cells with an oncolytic virus armed with the chemokine RANTES and the cytokine IL15, reasoning that the modified oncolytic virus will both have a direct lytic effect on infected malignant cells and facilitate migration and survival of CAR-T cells. Using neuroblastoma as a tumor model, we found that the adenovirus Ad5Δ24 exerted a potent, dose-dependent, cytotoxic effect on tumor cells, whereas CAR-T cells specific for the tumor antigen GD2 (GD2.CAR-T cells) were not damaged. When used in combination, Ad5Δ24 directly accelerated the caspase pathways in tumor cells exposed to CAR-T cells, whereas the intratumoral release of both RANTES and IL15 attracted CAR-T cells and promoted their local survival, respectively, increasing the overall survival of tumor-bearing mice. These preclinical data support the use of this innovative biologic platform of immunotherapy for solid tumors. Cancer Res; 74(18); 5195-205. ©2014 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokines / immunology
  • Disease Models, Animal
  • Immunotherapy / methods*
  • Mice
  • Mice, Inbred NOD
  • Microscopy, Confocal
  • Neuroblastoma / immunology*
  • Neuroblastoma / therapy*
  • Neuroblastoma / virology
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / immunology*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*
  • Xenograft Model Antitumor Assays


  • Cytokines
  • Receptors, Antigen, T-Cell