Armed Oncolytic Adenovirus-Expressing PD-L1 Mini-Body Enhances Antitumor Effects of Chimeric Antigen Receptor T Cells in Solid Tumors

Cancer Res. 2017 Apr 15;77(8):2040-2051. doi: 10.1158/0008-5472.CAN-16-1577. Epub 2017 Feb 24.


Chimeric antigen receptor-modified T cells (CAR T cells) produce proinflammatory cytokines that increase expression of T-cell checkpoint signals such as PD-L1, which may inhibit their functionality against solid tumors. In this study, we evaluated in human tumor xenograft models the proinflammatory properties of an oncolytic adenovirus (Onc.Ad) with a helper-dependent Ad (HDAd) that expresses a PD-L1 blocking mini-antibody (mini-body; HDPDL1) as a strategy to enhance CAR T-cell killing. Coadministration of these agents (CAd-VECPDL1) exhibited oncolytic effects with production of PD-L1 mini-body locally at the tumor site. On their own, HDPDL1 exhibited no antitumor effect and CAd-VECPDL1 alone reduced tumors only to volumes comparable to Onc.Ad treatment. However, combining CAd-VECPDL1 with HER2.CAR T cells enhanced antitumor activity compared with treatment with either HER2.CAR T cells alone or HER2.CAR T cells plus Onc.Ad. The benefits of locally produced PD-L1 mini-body by CAd-VECPDL1 could not be replicated by infusion of anti-PD-L1 IgG plus HER2.CAR T cells and coadministration of Onc.Ad in an HER2+ prostate cancer xenograft model. Overall, our data document the superiority of local production of PD-L1 mini-body by CAd-VECPDL1 combined with administration of tumor-directed CAR T cells to control the growth of solid tumors. Cancer Res; 77(8); 2040-51. ©2017 AACR.

Publication types

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

MeSH terms

  • A549 Cells
  • Adenoviridae / genetics
  • Adenoviridae / immunology*
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology
  • Cell Line, Tumor
  • Female
  • Hep G2 Cells
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Neoplasms / virology
  • Oncolytic Virotherapy / methods*
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Fusion Proteins / immunology*
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins