Radiofrequency ablation combined with KS-IL2 immunocytokine (EMD 273066) results in an enhanced antitumor effect against murine colon adenocarcinoma

Erik E. Johnson, Brett H. Yamane, Ilia N. Buhtoiarov, Hillary D. Lum, Alexander L. Rakhmilevich, David M. Mahvi, Stephen D. Gillies, Paul M. Sondel

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33 Scopus citations

Abstract

Purpose: Radiofrequency ablation (RFA) is a common treatment modality for surgically unresectable tumors. However, there is a high rate of both local and systemic recurrence. Experimental Design: In this preclinical study, we sought to enhance the antitumor effect of RFA by combining it with huKS-IL2 immunocytokine [tumor-specific monoclonal antibody fused to interleukin-2 (IL2)] in mice bearing CT26-KS colon adenocarcinoma. Mice were treated with RFA, huKS-IL2 via intratumoral injection, or combination therapy. Results: Treatment of mice bearing s.c. tumors with RFA and huKS-IL2 resulted in significantly greater tumor growth suppression and enhanced survival compared with mice treated with RFA or huKS-IL2 alone. When subtherapeutic regimens of RFA or huKS-IL2 were used, tumors progressed in all treated mice. In contrast, the combination of RFA and immunocytokine resulted in complete tumor resolution in 50% of mice. Treatment of a tumor with RFA and intratumoral huKS-IL2 also showed antitumor effects against a distant untreated tumor. Tumor-free mice after treatment with RFA and huKS-IL2 showed immunologic memory based on their ability to reject subsequent challenges of CT26-KS and the more aggressive parental CT26 tumors. Flow cytometry analysis of tumor-reactive T cells from mice with complete tumor resolution showed that treatment with RFA and huKS-IL2 resulted in a greater proportion of cytokineproducing CD4 T cells and CD8 T cells compared with mice treated with RFA or huKS-IL2 alone. Conclusions: These results show that the addition of huKS-IL2 to RFA significantly enhances the antitumor response in this murine model, resulting in complete tumor resolution and induction of immunologic memory.

Original languageEnglish (US)
Pages (from-to)4875-4884
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number15
DOIs
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Johnson, E. E., Yamane, B. H., Buhtoiarov, I. N., Lum, H. D., Rakhmilevich, A. L., Mahvi, D. M., Gillies, S. D., & Sondel, P. M. (2009). Radiofrequency ablation combined with KS-IL2 immunocytokine (EMD 273066) results in an enhanced antitumor effect against murine colon adenocarcinoma. Clinical Cancer Research, 15(15), 4875-4884. https://doi.org/10.1158/1078-0432.CCR-09-0110