Kevin Beccaria1, Aria Sabbagh1, John de Groot2, Michael Canney3, Alexandre Carpentier4, Amy B Heimberger5,6. 1. Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. 2. Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. 3. CarThera, Institut du Cerveau Et de La Moelle épinière (ICM), 75013, Paris, France. 4. Department of Neurosurgery, Sorbonne Université, UPMC Univ Paris 06, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires La Pitié-Salpêtrière, Paris, France. 5. Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. aheimber@mdanderson.org. 6. Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Unit 422, P.O. Box 301402, Houston, TX, 77230-1402, USA. aheimber@mdanderson.org.
Abstract
INTRODUCTION: Opening of the blood-brain barrier (BBB) by pulsed low intensity ultrasound has been developed during the last decade and is now recognized as a safe technique to transiently and repeatedly open the BBB. This non- or minimally invasive technique allows for a targeted and uniform dispersal of a wide range of therapeutic substances throughout the brain, including immune cells and antibodies. METHODS: In this review article, we summarize pre-clinical studies that have used BBB-opening by pulsed low intensity ultrasound to enhance the delivery of immune therapeutics and effector cell populations, as well as several recent clinical studies that have been initiated. Based on this analysis, we propose immune therapeutic strategies that are most likely to benefit from this strategy. The literature review and trial data research were performed using Medline/Pubmed databases and clinical trial registry www.clinicaltrials.gov . The reference lists of all included articles were searched for additional studies. RESULTS: A wide range of immune therapeutic agents, including small molecular weight drugs, antibodies or NK cells, have been safely and efficiently delivered to the brain with pulsed low intensity ultrasound in preclinical models, and both tumor control and increased survival have been demonstrated in different types of brain tumor models in rodents. Ultrasound-induced BBB disruption may also stimulate innate and cellular immune responses. CONCLUSIONS: Ultrasound BBB opening has just recently entered clinical trials with encouraging results, and the association of this strategy with immune therapeutics creates a new field of brain tumor treatment.
INTRODUCTION: Opening of the blood-brain barrier (BBB) by pulsed low intensity ultrasound has been developed during the last decade and is now recognized as a safe technique to transiently and repeatedly open the BBB. This non- or minimally invasive technique allows for a targeted and uniform dispersal of a wide range of therapeutic substances throughout the brain, including immune cells and antibodies. METHODS: In this review article, we summarize pre-clinical studies that have used BBB-opening by pulsed low intensity ultrasound to enhance the delivery of immune therapeutics and effector cell populations, as well as several recent clinical studies that have been initiated. Based on this analysis, we propose immune therapeutic strategies that are most likely to benefit from this strategy. The literature review and trial data research were performed using Medline/Pubmed databases and clinical trial registry www.clinicaltrials.gov . The reference lists of all included articles were searched for additional studies. RESULTS: A wide range of immune therapeutic agents, including small molecular weight drugs, antibodies or NK cells, have been safely and efficiently delivered to the brain with pulsed low intensity ultrasound in preclinical models, and both tumor control and increased survival have been demonstrated in different types of brain tumor models in rodents. Ultrasound-induced BBB disruption may also stimulate innate and cellular immune responses. CONCLUSIONS: Ultrasound BBB opening has just recently entered clinical trials with encouraging results, and the association of this strategy with immune therapeutics creates a new field of brain tumor treatment.
Entities:
Keywords:
Blood–brain barrier; Drug delivery; Immunotherapy; Low intensity pulsed ultrasound
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