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Use of neutrophil gelatinase-associated lipocalin to promote crossing of therapeutic antibodies across blood-brain barrier

A technology of lipocalin and neutrophils, which is applied in the field of tumor treatment, can solve the problems such as the difficulty of large-scale complete resection of surgery, and achieve the effects of strong clinical transformation significance, improved effect, and good therapeutic effect

Pending Publication Date: 2021-03-16
GENERAL HOSPITAL OF TIANJIN MEDICAL UNIV
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Problems solved by technology

[0002] Brain tumors include primary brain tumors and brain metastases. The best treatment method is complete surgical resection. However, due to the unresectable nature of normal brain tissue and the characteristics of extensive invasive growth of malignant tumors into the brain, large-scale complete surgical resection is required. extremely difficult

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  • Use of neutrophil gelatinase-associated lipocalin to promote crossing of therapeutic antibodies across blood-brain barrier
  • Use of neutrophil gelatinase-associated lipocalin to promote crossing of therapeutic antibodies across blood-brain barrier
  • Use of neutrophil gelatinase-associated lipocalin to promote crossing of therapeutic antibodies across blood-brain barrier

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Embodiment Construction

[0017] The present invention will be further technically described below with reference to the accompanying drawings and examples.

[0018] 1. Synthesis of Monoclonal Antibody (mAb) Nanocapsules

[0019] Cetuximab solution (ERBITUX, Merck, Darmstadt, Germany) (5 mg / mL) was diluted to 1 mg / mL with phosphate buffer (20 mM, pH=7.4) in an ice bath. N-(3-aminopropyl)methacrylamide (APM) was added to the antibody solution and mixed at 4°C for 10 minutes. 2-Methacryloyloxyethylphosphorylcholine (MPC) monomer and diallyl disulfide (DADS) were then added to the solution. The molar ratio of MPC:APM:crosslinker was adjusted to 50:5:1. Ammonium persulfate (APS) and N,N,N,N'-tetramethyldiamine (TEMED) were then added to the reaction solution to initiate radical polymerization. Polymerization was performed under nitrogen at 4°C for 2 hours to form nanocapsules. The synthesized nanocapsules were purified with a hydrophobic interaction column (Phenyl-Sepharose 4BCL) and dialyzed against P...

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Abstract

The invention discloses a use of neutrophil gelatinase-associated lipocalin in promoting a therapeutic antibody to cross a blood-brain barrier. The therapeutic antibody is a nanocapsule containing immune globulin. The neutrophil gelatinase-associated lipocalin enters blood through intravenous injection to play a role in increasing the permeability of a blood-brain barrier. According to the presentinvention, lipoprotein related to neutrophil gelatinase is intravenously injected into blood circulation of a glioma animal model, the permeability of a blood-brain barrier can be improved, and therefore the total amount of therapeutic antibodies crossing the blood-brain barrier is increased, and particularly, when the therapeutic antibodies select nanocapsules containing immune globulin, the effect that the medicine passes through the blood-brain barrier can be further improved, a better treatment effect is achieved, and extremely high clinical transformation significance is achieved.

Description

technical field [0001] The invention relates to the technical field of tumor treatment, in particular to the use of neutrophil gelatinase-associated lipocalin in promoting therapeutic antibodies to cross the blood-brain barrier. Background technique [0002] Brain tumors include primary brain tumors and brain metastases. The best treatment method is complete surgical resection. However, due to the unresectable nature of normal brain tissue and the characteristics of extensive invasive growth of malignant tumors into the brain, large-scale complete surgical resection is required. extremely difficult. Therefore, except for some brain tumor patients who have surgical indications and can choose surgery, other brain tumor patients are mostly treated with drugs. [0003] The most significant obstacle to the adoption of drugs to treat brain tumors is the delivery of therapeutic antibodies (tAbs) to the central nervous system (CNS). The blood-brain barrier separates the central ne...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K47/42A61K9/51A61P35/00
CPCC07K16/2863A61K47/42A61K9/5169A61P35/00A61K2039/505
Inventor 康春生原续波杨超王琦雪王琳
Owner GENERAL HOSPITAL OF TIANJIN MEDICAL UNIV
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