Mar 27, 2020

Oncolytic vaccinia virus delivering tethered IL-12 enhances antitumor effects with improved safety

Journal for Immunotherapy of Cancer
Yan GeDavid L Bartlett


Immune checkpoint blockade is arguably the most effective current cancer therapy approach; however, its efficacy is limited to patients with "hot" tumors, warranting an effective approach to transform "cold" tumors. Oncolytic viruses (especially properly armed ones) have positive effects on almost every aspect of the cancer-immunity cycle and can change the cancer-immune set point of a tumor. Here, we tested whether oncolytic vaccinia virus delivering tethered interleukin 12 (IL-12) could turn a "cold" tumor into a "hot" tumor while avoiding IL-12's systemic toxicity. Our data demonstrated that tethered IL-12 could be maintained in the tumor without treatment-induced toxic side effects. Moreover, the treatment facilitated tumor infiltration of more activated CD4+ and CD8+ T cells and less Tregs, granulocytic myeloid-derivedsuppressor cells, and exhausted CD8+ T cells, with increased interferon γ and decreased transforming growth factor β, cyclooxygenase-2, and vascular endothelial growth factor expression, leading to transformed, immunogenic tumors and improved survival. Combined with programmed cell death 1 blockade, vaccinia virus expressing tethered IL-12 cured all mice with late-stage colon cancer, suggesting immediate tran...Continue Reading

  • References28
  • Citations


  • References28
  • Citations


  • This paper may not have been cited yet.

Mentioned in this Paper

Cyclooxygenase 2
CD8-Positive T-Lymphocytes
Vaccinia virus
CD4 Positive T Lymphocytes
Transforming Growth Factor beta
Oncolytic Viruses
Cancer Treatment

Related Feeds

Cancer Immunotherapy

Cancer immunotherapy is an important field of research that is looking at controlling cancer and tumor growth by activating the individuals own immune system. Recent studies have utilized chimeric antigen receptor t-cell therapy, immune checkpoint inhibitors and neoantigen vaccines. Discover the latest research on cancer immunotherapy here.