Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Bacterially derived, intact minicells for delivery of therapeutic agents to brain tumors

A technology for microcells and brain tumors, which can be used in preparations for in vivo experiments, capsule delivery, anti-tumor drugs, etc., and can solve problems such as poor cure rate of brain cancer treatment.

Inactive Publication Date: 2014-10-22
ENGENEIC MOLECULAR DELIVERY PTY LTD
View PDF12 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Despite Decades of Extensive Efforts, Cure Rates in Brain Cancer Treatment Are Terribly Poor

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Bacterially derived, intact minicells for delivery of therapeutic agents to brain tumors
  • Bacterially derived, intact minicells for delivery of therapeutic agents to brain tumors
  • Bacterially derived, intact minicells for delivery of therapeutic agents to brain tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0201] Example 1. Preparation of doxorubicin-coated minicells targeting canine EGFR

[0202] Minicells were derived from Salmonella typhi, a minCDE-chromosomal deletion mutant of S. typhimurium, purified, coated with doxorubicin (dox) and treated with bispecifics including anti-minicell surface O-glycan and anti-canine EGFR specificities Linked targeting of monoclonal antibodies (MAbs), (named EGFR microcell 阿霉素 ), as previously described by MacDiarmid et al. (2007).

[0203] Characterize first EGFR microcell 阿霉素 Their suitability for intravenous administration to seven dogs with advanced brain cancer (dogs designated BCD-1 to BCD-7). Two additional dogs, BCD-8 and BCD-9, presented to the veterinary care center but were not studied because of more advanced brain tumors and were euthanized. Brain biopsy samples provided respective brain tumor cells for in vitro studies.

Embodiment 2

[0204] Example 2. Characterization of anti-human EGFR monoclonal antibodies that bind to canine brain tumor cells

[0205] Upregulation and overexpression of EGFR is well known in -60% of GBM cases in humans (Smith et al., 2001) and dogs (Higgins et al., 2010). Given the non-availability of specific canine EGFR monoclonal antibodies, commercially available anti-human EGFR MAbs were tested in canine and human brain tumor cell lines to determine the cross-reactivity of the MAbs to EGFR on canine brain tumor cells.

[0206] Where feasible, brain tumor biopsy samples were obtained from case study dogs. Tissue samples from BCD-1, -8, and -9 were treated with 1 mg / ml of Dulbecco's modified Eagle's medium (DMEM) medium containing 10% fetal calf serum (FCS) and streptomycin. Collagenase treatment for 10min. Undigested tissue was removed by filtration through double sheets of sterile gauze. Collagenase digestion was stopped by diluting the cells with 5 ml of medium and centrifuging ...

Embodiment 3

[0215] Example 3. Determination of the sensitivity of canine brain cancer cells to the chemotherapeutic drug doxorubicin

[0216] Before treating dogs with advanced brain cancer with doxorubicin-encapsulated, EGFR-targeted minicells, it is important to determine whether canine brain tumor cells are sensitive or resistant to the chemotherapeutic drug doxorubicin.

[0217] Canine brain tumor cells BCD-1, -8, -9 and J3T and human brain tumor cell line U87-MG were inoculated in a 96-well plate, 5x 10 per well 3 cells. at 37°C, 5% CO 2 The next cells were incubated overnight.

[0218] Doxorubicin was added to the cells in 100 μL of relevant media containing serum concentrations ranging from 1.7 nM to 8,600 nM and incubated for 72 hours.

[0219] To measure the cytotoxic effect of doxorubicin, an MTS cell proliferation assay was performed. 20uL of MTS solution (CellTitre Aqueous One MTS reagent - Promega) was added to each well and incubated for 30 minutes in the dark. Absorb...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
diameteraaaaaaaaaa
molecular weightaaaaaaaaaa
Login to View More

Abstract

Systemic administration of intact, bacterially derived minicells results in rapid accumulation of the minicells in the microenvironment of a brain tumor, in therapeutically significant concentrations, without requiring endothelial endocytosis / transcytosis across the blood brain barrier or any other mechanism by which, pursuant to conventional approaches, nanoparticles have entered into that microenvironment. Accordingly, a wide variety of brain tumors, both primary and metastatic, can be treated by administering systemically a therapeutically effective amount of a composition comprised of a plurality of such minicells, each minicell being a vehicle for an active agent against the tumor, such as a radionuclide, a functional nucleic acid or a plasmid encoding one, or a chemotherapeutic agent.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 61 / 569,907, filed December 13, 2011, the contents of which are hereby incorporated by reference in their entirety. Background technique [0003] Primary brain tumors consist of a diverse group of tumors derived from a number of different cell lines. According to the World Health Organization classification (Louis et al., 2007), tumors of the central nervous system are classified as astrocytic, oligodendrocytes, or a mixture thereof (oligoastrocytic). These tumors are further classified by subtype and graded from I to IV based on histology, with grade IV being the most aggressive. Glioblastoma multiforme (GBM), the most aggressive form of primary malignant brain tumors, accounts for approximately 45% to 50% of all primary brain tumors (Wrensch et al., 2002; Behin et al., 2003) and represents the second leading cause of cancer death among adults un...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61P35/00
CPCA61K47/48561A61K51/1203A61K47/46A61K9/5068A61K47/6849A61P35/00A61P35/04A61P43/00A61P9/00A61K51/08A61K51/0491A61K51/1027A61K51/109A61K51/1045A61K47/6901A61K31/713A61K45/06A61K35/66
Inventor H·布拉姆巴特J·麦克迪尔米德
Owner ENGENEIC MOLECULAR DELIVERY PTY LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com