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Hdm-2 targeting compositions cause tumor cell necrosis rather than apoptosis of cancer cells

a technology of hdm2 and composition, which is applied in the direction of peptide sources, p53 proteins, instruments, etc., can solve the problems of limited p53-targeting cancer treatments and ineffective p53-targeting cancer treatments at treating various types of cancer

Inactive Publication Date: 2020-01-02
THE RES FOUND OF STATE UNIV OF NEW YORK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0019]The method may further include the step of classifying an identified cancer cell as a type of cancer. This may be done in vivo, as part of a diagnostic for cancer. Alternatively, the fluorescent-labeled MRP attached to an HDM-2 targeting component or HDM-2 recognition agent may be administered to a candidate surgical area. Such a use may provide derivative identifiers to a surgeon of the highly cancerous tissue, less cancerous tissue, and non-cancerous tissue for surgical removal and / or intervention purposes. As such, the embodiments and features of the present invention may provide a great aid in surgical pathology, helping pathologists to distinguish cancer from non-cancer.

Problems solved by technology

Thus, these p53 targeting cancer treatments are limited since they do not cause cell death in these types of cancer cells.
Thus, p53-targeting cancer treatments are ineffective at treating various types of cancer.

Method used

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  • Hdm-2 targeting compositions cause tumor cell necrosis rather than apoptosis of cancer cells
  • Hdm-2 targeting compositions cause tumor cell necrosis rather than apoptosis of cancer cells
  • Hdm-2 targeting compositions cause tumor cell necrosis rather than apoptosis of cancer cells

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Materials and Methods

[0143]Peptides.

[0144]The following peptides were synthesized by solid phase methods and were purified to >95% purity (Biopeptides Corp, La Jolla, Calif.): PNC-27 containing residues 12-26 (PPLSQETFSDLWKLL) (SEQ ID NO: 8) from the hdm-2 binding domain of p53 and PNC-28 (ETFSDLWKLL) (SEQ ID NO: 32) containing residues 17-26 from the hdm-2 binding domain of p53, both attached on their carboxyl terminal ends to the transmembrane-penetrating sequence which is related to the reverseomer sequence of the antennapedia sequence, KKWKMRRNQFWVKVQRG (SEQ ID NO: 1), also called MRP; the control peptide PNC-26, containing only residues 12-26 of p53 and no MRP; the control peptide PNC-29, an unrelated peptide from cytochrome P450 (also called X13) (bold) attached to MRP (italics), whose sequence is MPFSTGKRIMLGEKKWKMRRNQFWVKVQRG (SEQ ID NO: 4); and PNC-7, a peptide from the ras-p21 protein containing ras-p21 residues 35-47 (TIEDSYRKQVVID) (SEQ ID NO: 7) attached to the MRP havi...

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Abstract

An aspect of the invention provides a method of selectively necrosing cells, comprising: providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell; and administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component attached to the HDM-2 targeting component, wherein said compound comprises a membrane-active form.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This patent application is a continuation of U.S. patent application Ser. No. 14 / 470,488, filed Aug. 27, 2014, which is a continuation of U.S. patent application Ser. No. 13 / 122,256, filed Sep. 14, 2011, which is the national stage filing of International Patent Application No. PCT / US2009 / 059380, filed Oct. 2, 2009, which claims the benefit of and priority to U.S. Provisional Patent Application Ser. No. 61 / 102,590 filed on Oct. 3, 2008, the contents of which are incorporated herein by reference in their entirety.FUNDING STATEMENT[0002]This invention was made with government support by a Veteran's Administration Grant (WBB) and The American College of Surgeon's Faculty Research Fellowship Award 2007-2009 (WBB).FIELD OF THE INVENTION[0003]The invention relates to methods of effectively treating various forms of cancer and screening candidate cancer treatments and compounds. Specifically, the present invention is directed to the use of novel...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/47G01N33/50G01N33/574
CPCC07K14/4746G01N2333/904G01N2500/10G01N33/57484G01N2333/4748G01N33/5011A61K45/06G01N33/57407G01N33/57492A61P35/00A61K38/02C07K2/00
Inventor PINCUS, MATTHEW R.MICHL, JOSEFSARAFRAZ-YAZDI, EHSAN
Owner THE RES FOUND OF STATE UNIV OF NEW YORK
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