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

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 cytokine-producing 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.

• Authors: Erik E Johnson, Brett H Yamane, Ilia N Buhtoiarov, Hillary D Lum, Alexander L Rakhmilevich, David M Mahvi, Stephen D Gillies, Paul M Sondel
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 15 Pg. 4875-84 (Aug 01 2009) ISSN: 1557-3265 [Electronic] United States
• PMID: 19638464 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Interleukin-2
• tucotuzumab celmoleukin

Topics

• Adenocarcinoma (immunology, therapy)
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Catheter Ablation
• Cell Line, Tumor
• Colonic Neoplasms (immunology, therapy)
• Combined Modality Therapy
• Female
• Immunologic Memory (drug effects, immunology)
• Interleukin-2 (analogs & derivatives, therapeutic use)
• Mice
• Mice, Inbred BALB C