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In situ vaccination with laser interstitial thermal therapy augments immunotherapy in malignant gliomas

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Abstract

Introduction

Laser interstitial thermal therapy (LITT) remains a promising advance in the treatment of primary central nervous system malignancies. As indications for its use continue to expand, there has been growing interest in its ability to induce prolonged blood brain barrier (BBB) permeability through hyperthermia, potentially increasing the effectiveness of current therapeutics including BBB-impermeant agents and immunotherapy platforms.

Methods

In this review, we highlight the mechanism of hyperthermic BBB disruption and LITT-induced immunogenic cell death in preclinical models and humans. Additionally, we summarize ongoing clinical trials evaluating a combination approach of LITT and immunotherapy, which will likely serve as the basis for future neuro-oncologic treatment paradigms.

Results

There is evidence to suggest a highly immunogenic response to laser interstitial thermal therapy through activation of both the innate and adaptive immune response. These mechanisms have been shown to potentiate standard methods of oncologic care. There are only a limited number of clinical trials are ongoing to evaluate the utility of LITT in combination with immunotherapy.

Conclusion

LITT continues to be studied as a possible technique to bridge the gap between exciting preclinical results and the limited successes seen in the field of neuro-oncology. Preliminary data suggests a substantial benefit for use of LITT as a combination therapy in several clinical trials. Further investigation is required to determine whether or not this treatment paradigm can translate into long-term durable results for primary intracranial malignancies.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of Florida, Gainesville, FL, USA

    David H. Shin, Kaitlyn F. Melnick, David D. Tran & Ashley P. Ghiaseddin

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  1. David H. Shin
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  2. Kaitlyn F. Melnick
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  3. David D. Tran
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  4. Ashley P. Ghiaseddin
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Corresponding authors

Correspondence to David H. Shin or Ashley P. Ghiaseddin.

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Conflicts of interest

David H. Shin declares that he has no conflict of interest. Kaitlyn F. Melnick declares that she has no conflict of interest. David D. Tran is one of the primary investigators in the referenced trial at this institution (NCT02311582). David D. Tran also has received grant funding from Celldex, NWBiotech, Novocure, and Merck. David D. Tran has received personal fees from Novocure and prIME Oncology. Ashley P. Ghiaseddin has received personal fees from Monteris Medical. Ashley P. Ghiaseddin has also received research funding support from Orbus Therapeutics.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Shin, D.H., Melnick, K.F., Tran, D.D. et al. In situ vaccination with laser interstitial thermal therapy augments immunotherapy in malignant gliomas. J Neurooncol 151, 85–92 (2021). https://doi.org/10.1007/s11060-020-03557-x

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