4.6 Article

Local therapy with an engineered oncolytic adenovirus enables antitumor response in non-injected melanoma tumors in mice treated with aPD-1

期刊

ONCOIMMUNOLOGY
卷 11, 期 1, 页码 -

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2022.2028960

关键词

Oncolytic adenovirus; immunotherapy; TNFa; IL-2; aPD-1; lymphocytes; melanoma

资金

  1. Suomen Kulttuurirahasto [00200899]
  2. Jane and Aatos Erkko Foundation
  3. HUCH Research Funds (VTR)
  4. Finnish Cancer Organizations
  5. University of Helsinki
  6. Novo Nordisk Foundation
  7. Paivikki and Sakari Sohlberg Foundation
  8. TILT Biotherapeutics Ltd
  9. HBGS
  10. GSBM

向作者/读者索取更多资源

This study demonstrates that the combination treatment of local injection of adenovirus coding for TNFa and IL-2 and systemic aPD-1 therapy can effectively control both injected and non-injected tumors in animal models. The treatment reshapes the tumor microenvironment and enhances the systemic antitumor response.
Intratumoral immunotherapies are entering clinical use but concerns remain regarding their effects on non-injected tumors. Here, we studied the impact of local treatment with an adenovirus coding for TNFa and IL-2 on systemic antitumor response in animals receiving aPD-1 (anti-programmed cell death protein 1) therapy. Using bilateral murine melanoma models, we tested systemic tumor response to combined therapy with anti-PD-1 and an adenovirus coding for TNFa and IL-2 (virus). Virus was given intratumorally (to one of the two tumors only) and aPD-1 monoclonal antibody systemically. We evaluated both tumors' response to treatment, overall survival, metastasis development, and immunological mechanisms involved with response. Consistent tumor control was observed in both injected and non-injected tumors, including complete response in all treated animals receiving aPD-1+ virus therapy. Mechanistically, virus injections enabled potent effector lymphocyte response locally, with systemic effects in non-injected tumors facilitated by aPD-1 treatment. Moreover, adenovirus therapy demonstrated immunological memory formation. Virus therapy was effective in preventing metastasis development. Local treatment with TNFa and IL-2 coding adenovirus enhanced systemic response to aPD-1 therapy, by re-shaping the microenvironment of both injected and non-injected tumors. Therefore, our pre-clinical data support the rationale for a trial utilizing a combination of aPD-1 plus virus for the treatment of human cancer.

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