Volume 3 Supplement 2

30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)

Open Access

Potentiation of anti-glioma immunity induced by oncolytic adenovirus Delta-24-RGD through viral expression of immune co-stimulator OX40 ligand

  • Hong Jiang1,
  • Karen Dwyer2,
  • Laura Bover1,
  • Frederick Lang1,
  • Candelaria Gomez-Manzano1 and
  • Juan Fueyo1
Journal for ImmunoTherapy of Cancer20153(Suppl 2):P337

DOI: 10.1186/2051-1426-3-S2-P337

Published: 4 November 2015

Background

Oncolytic viruses are promising alternative cancer therapies that can cause anti-cancer immunity. We found Delta-24-RGD, an oncolytic adenovirus currently undergoing Phase I clinical trial in patients with recurrent glioblastomas, induced anti-glioma immunity in an immunpcompetent mouse model. We hypothesized that the anti-cancer immunity mediated by the virus could be augmented through expressing the immune co-stimulator OX40 ligand (OX40L) by the virus to enhance the antigen-presenting function of the cancer cells.

Methods

Thus we constructed Delta-24-RGDOX which included an OX40L-expressing cassette in the backbone of Delta-24-RGD. The new virus expressed OX40L efficiently in cultured cancer cells and in implanted glioma cells in mice while kept the same replication efficiency as Delta-24-RGD.

Results

Like its precedessor Delta-24-RGD, Delta-24-RGDOX induced immunogenic cell death in glioma cells. Importantly, compared to Delta-24-RGD, Delta-24-RGDOX induced enhanced anti-glioma activity in immunocompetent glioma models (means: 28.5 versus 17 days, P < .0001) but not in an immunodeficient model. Since glioma cells expressed high levels of PD-L1, we combined Delta-24-RGDOX with anti-PD-L1 antibody. Impressively, it resulted in 100% long-term survival in the treated mice while the virus alone only induced 25% long-term survival (P = 0.001). Further studies revealed that Delta-24-RGDOX induced higher levels of lymphocyte infiltration at the tumor sits (P < .001), greater anti-tumor activity of the lymphocytes (P < .05) and proliferation of tumor-associated antigen specific lymphocytes (P = .0002) than Delta-24-RGD.

Conclusions

Collectively, our data demonstrate that oncolytic viruses carrying immune co-stimulatory ligands and its combination with antibodies mainly targeted to cancer cells may constitute powerful and safer alternatives to the antibodies and other strategies targeting immune checkpoints in cancer therapy and warrant the development of clinical trials in cancer patients in the near future.

Authors’ Affiliations

(1)
MD Anderson Cancer Center
(2)
UT MD Anderson Cancer Center

Copyright

© Jiang et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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