Targeting immunoliposomes to EGFR-positive glioblastoma

ESMO Open

article

B. Kasenda¹  D. König¹  M. Manni³  R. Ritschard³  U. Duthaler⁴  E. Bartoszek³  A. Bärenwaldt³  S. Deuster⁵  G. Hutter⁶  D. Cordier⁶  L. Mariani⁶  J. Hench⁷  S. Frank⁷  S. Krähenbühl⁴  A. Zippelius¹  C. Rochlitz¹  C. Mamot⁸  A. Wicki¹  H. Läubli¹ 

[1] Division of Oncology, Department of Internal Medicine, University Hospital Basel;University of Basel;Department of Biomedicine, University Hospital and University of Basel;Division of Clinical Pharmacology, University Hospital Basel;Hospital Pharmacy, University Hospital Basel;Neurosurgery, University Hospital Basel;Institute of Pathology, University Hospital Basel;Division of Medical Oncology, Cantonal Hospital

关键词: nanomedicine;    blood–brain barrier;    targeted therapy;    pharmacokinetic;    cerebrospinal fluid;   

DOI  :  10.1016/j.esmoop.2021.100365

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background We assessed the capacity of epidermal growth factor receptor (EGFR)-targeted immunoliposomes to deliver cargo to brain tumor tissue in patients with relapsed glioblastoma harboring an EGFR amplification. We aimed to assess the tolerability and effectiveness of anti-EGFR immunoliposomes loaded with doxorubicin (anti-EGFR ILs-dox) in glioblastoma multiforme patients.Patients and methods Patients with EGFR-amplified, relapsed glioblastoma were included in this phase I pharmacokinetic trial. Patients received up to four cycles of anti-EGFR ILs-dox. Twenty-four hours later, plasma and cerebrospinal fluid (CSF) samples were obtained. In addition, we also treated three patients with anti-EGFR ILs-dox before resection of their relapsed glioblastoma. Doxorubicin concentrations were measured in plasma, CSF, and tumor tissue. Safety and efficacy parameters were also obtained.Results There were no or negligible levels of doxorubicin found in the CSF demonstrating that anti-EGFR ILs-dox are not able to cross the blood–brain barrier (BBB). However, significant levels were detected in glioblastoma tissue 24 h after the application, indicating that the disruption of BBB integrity present in high-grade gliomas might enable liposome delivery into tumor tissue. No new safety issues were observed. The median progression-free survival was 1.5 months and the median overall survival was 8 months. One patient undergoing surgery had a very long remission suggesting that neoadjuvant administration may have a positive effect on outcome.Conclusions We clearly demonstrate that anti-EGFR-immunoliposomes can be targeted to EGFR-amplified glioblastoma and cargo—in this case doxorubicin—can be delivered, although these immunoliposomes do not cross the intact BBB. (The GBM-LIPO trial was registered as NCT03603379).

【 授权许可】

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