Journal Article

NT-02EARLY TREATMENT OF HER2-AMPLIFIED BRAIN TUMOURS WITH TARGETED NK-92 CELLS AND FOCUSED ULTRASOUND IMPROVES SURVIVAL

Ryan Alkins, Alison Burgess, Giulio Francia, Robert Kerbel, Winfried Wels and Kullervo Hynynen

in Neuro-Oncology

Published on behalf of Society for Neuro-Oncology

Volume 16, issue suppl_5, pages v159-v159
Published in print November 2014 | ISSN: 1522-8517
Published online November 2014 | e-ISSN: 1523-5866 | DOI: http://dx.doi.org/10.1093/neuonc/nou265.2
NT-02EARLY TREATMENT OF HER2-AMPLIFIED BRAIN TUMOURS WITH TARGETED NK-92 CELLS AND FOCUSED ULTRASOUND IMPROVES SURVIVAL

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Malignant brain tumors have a dismal prognosis. Microscopic and often macroscopic residual remain after surgical resection, necessitating adjuvant chemo- and radiotherapy. Many intravenously delivered chemotherapeutic agents are hindered by the cerebral capillary endothelium and blood brain barrier (BBB), either due to their size, lipophilicity, or their interaction with efflux channels, resulting in modest treatment efficacy. Both those chemotherapeutic agents that cross the BBB and radiotherapy result in significant damage to healthy brain tissue. We previously demonstrated that targeted Natural Killer (NK-92) cells could be delivered to focal regions of the brain using a combination of focused ultrasound and Definity microbubbles. Targeted NK cells have advantages over other systemic therapies including their specific cytotoxicity to malignant cells, particularly those expressing the target antigen, in addition to sparing healthy cells and being unaffected by efflux channels. As such, once these cells gain access to the CNS, they can track to malignant tissues without inflicting collateral damage. We investigated whether multiple combined treatments of targeted NK-92 cells and focused ultrasound with microbubbles could slow tumor growth and improve survival in an orthotopic HER2-amplified rodent brain tumor model, using a human breast cancer line as a prototype. The HER2 receptor is expressed by a number of epithelial tumours including breast and glioblastoma. Breast cancers with HER2 amplification are more aggressive, have a higher risk of CNS metastasis, and poorer prognosis. We found that early intensive treatment with targeted NK-92 cells and ultrasound improved survival compared with bi-weekly treatments, or either treatment alone. The intensive treatment paradigm resulted in cure in 50% of subjects. Many tumour proteins could be exploited for targeted therapy with the NK-92 cell line, and combined with the mounting safety evidence for trans-cranial ultrasound, this may soon provide a non-invasive and highly targeted treatment option for patients with brain tumours.

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Subjects: Medical Oncology ; Neurology

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