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Therapy model for advanced intracerebral B16 mouse melanoma using radiation therapy combined with immunotherapy

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Abstract

A reproducible therapy model for advanced intracerebral B16 melanoma is reported. Implanted tumors (D0), suppressed by a single 15 Gy radiosurgical dose of 100 kVp X-rays (D8), were further suppressed by a single ip injection of a Treg-depleting mAb given 2 days prior to the initiation (D9) of four weekly then eight bi-monthly sc injections of GMCSF-transfected, mitotically disabled B16 cells. The trends of seven independent experiments were similar to the combined result: The median (days) [SD/total N] of survival went from 15[1.09/62] (no treatment control) to 35.8[8.8/58] (radiation therapy only) to 52.5[13.5/57] (radiation therapy plus immunotherapy). Within 2 weeks after immunization, tumors in mice receiving radiation therapy plus immunotherapy were significantly smaller than tumors in mice treated only with radiosurgery. Splenocytes and lymph node cells from immunized mice showed increased interferon γ production when cultured with syngeneic tumor cells. We suggest that our model will be useful for the development and testing of novel combination therapies for brain tumors.

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Acknowledgments

We thank Dr. Daniel N. Slatkin for his advice and the technical support he provided for some of these experiments.

Conflict of interest

The authors declare that they have no conflict of interest in any form with respect to this article.

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Authors and Affiliations

  1. Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030, USA

    Henry M. Smilowitz, Daniel Sasso & Edward W. Lee

  2. Department of Statistics, University of Connecticut, 215 Glenbrook Road, Storrs, CT, 06269-4120, USA

    Gyuhyeong Goh

  3. Medical Department, Brookhaven National Laboratory, Upton, NY, 11973, USA

    Peggy L. Micca

  4. Department of Radiation Oncology and Neurology, State University of New York, Stony Brook, NY, 11794-7028, USA

    F. Avraham Dilmanian

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  1. Henry M. Smilowitz
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  2. Daniel Sasso
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Correspondence to Henry M. Smilowitz.

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Smilowitz, H.M., Sasso, D., Lee, E.W. et al. Therapy model for advanced intracerebral B16 mouse melanoma using radiation therapy combined with immunotherapy. Cancer Immunol Immunother 62, 1187–1197 (2013). https://doi.org/10.1007/s00262-013-1423-9

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