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Methods and related compositions for the treatment of cancer

Inactive Publication Date: 2017-02-09
IMMIX A DIV OF CARLTON INTL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a composition that targets tumor cells and delivers a drug molecule to them. The composition includes a micelle construct, an antibody single chain fragment variable (scFv), a NF-kb inhibitor, and a topoisomerase II inhibitor. The scFv is attached to the micelle and the drug molecule is delivered to the tumor cells through intracellular delivery. The composition can be administered through intravenous injection and can treat various types of cancer, including brain, ovarian, and colon cancer. The molecular size of the composition is small, making it suitable for targeted delivery to tumor cells.

Problems solved by technology

Complete and effective treatment for cancer has not been developed despite billions of dollars being spent in cancer research.
This diversity, in turn, is part of what has made treatment of cancer so difficult, as a population of cancerous cells could easily include a mutant variety that happens to be resistant to any individual treatment or chemotherapy drug that is administered.

Method used

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  • Methods and related compositions for the treatment of cancer
  • Methods and related compositions for the treatment of cancer
  • Methods and related compositions for the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

example 1

Materials

[0043]1,2-Disteroyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (PEGPE) was from Avanti Polar Lipids (Alabaster, Ala., USA). pNp-PEG3400-pNP was purchased from Laysan Bio (Arab, Ala.). Curcumin (CUR), vitamin E and triethylamine (TEA) were purchased from Sigma (St. Louis, Mo., USA). Doxorubicin HCl (DOX) was from LC Laboratories (Woburn, Mass.). Accumax was from Innovative Cell Technologies, Inc. (San Diego, Calif.). The CellTiter-Glo luminescent cell viability assay kit was from Promega (Fitchburg, Wis.). All other reagents were of analytical grade. DOX free base was obtained by incubating DOX HCl (in methanol, 0.5 mg / ml) with 5-fold molar excess of TEA overnight. pNP-PEG3400-PE was synthesized in-house.

example 2

Micelle Preparation

[0044]DOX and / or CUR drug-loaded mixed micelles were prepared by the thin film hydration method. CUR (1 mg / ml in 0.1% acetic acid-methanol solution) and / or DOX free base (0.5 mg / ml in methanol solution) were added to PEG2000-PE solution in chloroform. Initial drug amounts were adjusted after the formulation optimization studies to result in CUR:DOX ratio of 32 (w / w). The organic solvents were removed by the rotary evaporation and a thin film of drugs / micelle-forming material mixture was formed. This film was further dried overnight in freeze-dryer to remove any residuals of organic solvents (Freezone 4.5 Freeze Dry System, Labconco, Kansas City, Mo.). Drug-loaded micelles were formed by resuspending the film in phosphate buffered saline (PBS) pH 7.2, to give the final concentration of micelle forming materials of 5 mM in all formulations. The micelle formulations were dialyzed 1 h against PBS pH 7.2 to remove excess of TEA. Excess non-incorporated drugs were separ...

example 3

GLUT-1 scFv Modified Micelle Cytotoxicity on Ovarian Cancer Cell Line

[0046]For cytotoxicity evaluations, A2780 human ovarian carcinoma (ATCC) and its Doxorubicin resistant derivative A2780 / Adr (ECACC) were used. A2780 cells were cultured in RPMI medium supplemented with 10% FBS and 1% penicillin-streptomycin. Drug resistant ovarian cancer cells were grown in same medium with the addition of 100 nM DOX.

[0047]The cells were seeded in 96-well plates at a density of 3000 cells / well or 5,000 cells / well for 48 or 24 hours treatment groups, respectively. The cells were treated with free drugs or micelle formulations containing 40 μM CUR and 0.8 μM DOX in serum complete RPMI medium. The cells were incubated 24 h and 48 h continuously in the continuous treatment groups. Additionally, in another treatment regimen the cells were incubated with drugs / micelles for 4 hours then washed and further incubated for 44 h. At the end of treatment times, the wells were washed twice with medium and then i...

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Abstract

Disclosed herein are compositions and nanoconjugates comprising a micelle construct; an antibody single chain fragment variable (scFv); a NF-kb inhibitor; and a topoisomerase II inhibitor. Further disclosed herein are methods of delivering a drug molecule to a tumor site of a subject comprising: attaching the drug molecule to a targeted micelle, wherein the targeted micelle comprises a micelle construct and an antibody single chain fragment variable (scFv); and delivering the drug molecule attached to the targeted micelle to the tumor site through intracellular delivery. Also disclosed herein are methods of treating cancer or inhibiting tumor cell growth comprising administering to a subject in need thereof, a therapeutically effective dosage of a composition comprising a micelle construct, an antibody single chain fragment variable (scFv), a NF-kb inhibitor, and a topoisomerase II inhibitor.

Description

RELATED APPLICATION[0001]This application claims the benefit of priority of U.S. patent application Ser. No. 14 / 385,140 filed on Sep. 12, 2014, which is a national stage of PCT / US2013 / 032153, filed on Mar. 15, 2013, which claims the benefit of U.S. Provisional Application Ser. No. 61 / 611,529 filed on Mar. 15, 2012 and US Provisional Application Ser. No. 61 / 701,018 filed on Sep. 14, 2012. This application further claims the benefit of priority of U.S. Provisional Patent Application No. 62 / 245,813, filed on Oct. 23, 2015. Each of these applications is incorporated by reference herein in its entirety.FIELD OF THE INVENTION[0002]The present disclosure relates to the field of medicine, and more specifically, the treatment of cancer.BACKGROUND OF THE DISCLOSURE[0003]Complete and effective treatment for cancer has not been developed despite billions of dollars being spent in cancer research. Part of the reason is because tumor cells can be made up of a variety of cell types, produced as th...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K9/107C07K16/28A61K31/12A61K31/704
CPCA61K47/48561A61K31/12A61K31/704C07K16/28A61K9/1075C07K2317/622A61K9/0019A61K45/06A61K47/24A61K47/6849C07K16/00C07K16/18A61K2300/00
Inventor RACHMAN, ILYA
Owner IMMIX A DIV OF CARLTON INTL
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