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Activation of local and systemic anti-tumor immune responses by ablation of solid tumors with intratumoral electrochemical or alpha radiation treatments

  • Focussed Research Review
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Cancer, the most devastating chronic disease affecting humankind, is treated primarily by surgery, chemotherapy, and radiation therapy. Surgery and radiotherapy are mainly used for debulking the primary tumor, while chemotherapy is the most efficient anti-metastatic treatment. To control better metastatic cancer, the host immune system should be stimulated. Yet, successful specific stimulation of the immune system against tumors was seldom achieved even in antigenic tumors. Our working hypothesis is that aggressive in situ tumor ablation can release tumor antigens and danger signals, which will enhance anti-tumor T cell responses resulting in the destruction of residual malignant cells in primary tumors and distant metastases. We developed two efficient in situ ablation treatments for solid cancer, which can be used to destroy the primary tumors and stimulate anti-tumor immune responses. The first treatment, electrochemical ablation, is applied through intratumoral electrodes, which deliver unipolar-pulsed electric currents. The second treatment, diffusing alpha-emitters radiation therapy (DaRT), is based on intratumoral 224Ra-loaded wire(s) that release by recoil its daughter atoms. These short-lived alpha-emitting atoms spread in the tumor and spray it with lethal alpha particles. It was confirmed that these treatments effectively destroy various malignant animal and human primary solid tumors. As a consequence of such tumor ablation, tumor-derived antigenic material was released and provoked systemic T cell-dependent anti-tumor immunological reactions. These reactions conferred protection against a secondary tumor challenge and destroyed remaining malignant cells in the primary tumor as well as in distant metastases. Such anti-tumor immune responses could be further amplified by the immune adjuvant, CpG. Electrochemical ablation or DaRT together with chemotherapy and immunostimulatory agents can serve as treatment protocols for solid metastatic tumors and can be applied instead of or in combination with surgery.

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Acknowledgments

This work was supported in part by The Roberts-Guthman Chair in Immunopharmacology, The German Israeli Fund, The Israel Cancer Association, and Althera Medical LTD.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. The Roberts-Guthman Chair in Immunopharmacology, Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, P.O. Box 39040, Tel Aviv, 69978, Israel

    Yona Keisari, Ilan Hochman & Hila Confino

  2. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ilan Hochman & Rafi Korenstein

  3. School of Physics and Astronomy, Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel

    Itzhak Kelson

Authors
  1. Yona Keisari
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  2. Ilan Hochman
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  4. Rafi Korenstein
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  5. Itzhak Kelson
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Corresponding author

Correspondence to Yona Keisari.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Third International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2013), held in Krakow, Poland, 22nd–25th April 2013. It is part of a CII series of Focussed Research Reviews and meeting report.

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Keisari, Y., Hochman, I., Confino, H. et al. Activation of local and systemic anti-tumor immune responses by ablation of solid tumors with intratumoral electrochemical or alpha radiation treatments. Cancer Immunol Immunother 63, 1–9 (2014). https://doi.org/10.1007/s00262-013-1462-2

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  • DOI: https://doi.org/10.1007/s00262-013-1462-2

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