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Compositions and Methods for Inhibiting Tumor Cells by Inhibiting the Transcription Factor ATF5

a transcription factor and tumor cell technology, applied in the direction of drug compositions, peptide sources, peptide/protein ingredients, etc., can solve the problems of brain tumor invasion, damage to normal tissue, impaired sensorimotor and cognitive function, etc., to promote apoptosis and treat and/or prevent tumors

Active Publication Date: 2017-08-24
RGT UNIV OF CALIFORNIA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The CP-d / n-ATF5 peptide effectively promotes apoptosis in glioblastoma cells, leading to tumor regression and eradication without apparent toxicity to normal cells, as demonstrated in both in vitro and in vivo models, offering a potential therapeutic approach for brain tumors.

Problems solved by technology

Brain tumors invade and destroy normal tissue, producing such effects as impaired sensorimotor and cognitive function, increased intracranial pressure, cerebral edema, and compression of brain tissue, cranial nerves, and cerebral vessels.

Method used

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  • Compositions and Methods for Inhibiting Tumor Cells by Inhibiting the Transcription Factor ATF5
  • Compositions and Methods for Inhibiting Tumor Cells by Inhibiting the Transcription Factor ATF5
  • Compositions and Methods for Inhibiting Tumor Cells by Inhibiting the Transcription Factor ATF5

Examples

Experimental program
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Effect test

Embodiment Construction

[0036]4.1 ATF5 & D / N-ATF5 Compositions

[0037]ATF5 is widely expressed by various tumor types. In particular, ATF5 is expressed not only in highly proliferative neural tumors, e.g., glioblastomas, but is also expressed in multiple neoplasias including, but not necessarily limited to: breast, ovary, endometrium, gastric, colon, liver, pancreas, kidney, bladder, prostate, testis, skin, esophagus, tongue, mouth, parotid, larynx, pharynx, lymph node, lung, hematological cancers, peripheral nervous system, and brain tumors.

[0038]As used herein, “ATF5” includes both an “ATF5 protein” and an “ATF5 analogue”. Unless otherwise indicated, “protein” shall include a protein, protein domain, polypeptide, or peptide, and any fragment thereof. The ATF5 protein has the amino acid sequence set forth in NCBI Accession No. NP_001180575 (human ATF5) or NCBI Accession No. NP_109618 (murine ATF5), including conservative substitutions thereof. As used herein, “conservative substitutions” are those amino aci...

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Abstract

The present invention relates to methods for treating and / or preventing tumors and / or promoting apoptosis in a neoplastic cell comprising contacting the neoplastic cell with an cell-penetrating dominant-negative ATF5 (“CP-d / n-ATF5”), wherein the CP-d / n-ATF5 is capable of inhibiting ATF5 function and / or activity.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 14 / 830,194, filed Aug. 19, 2015, which is a continuation of International Patent Application No. PCT / US2014 / 017550, filed Feb. 21, 2014, and claims priority to U.S. Provisional Application Ser. No. 61 / 768,390, filed Feb. 22, 2013, to all of which priority is claimed and the contents of which are incorporated herein in their entireties.STATEMENT OF GOVERNMENT INTEREST[0002]This invention was made with government support under Grant No. RCA126924A awarded by the National Institutes of Health. The government has certain rights in the invention.SEQUENCE LISTING[0003]The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jan. 13, 2017, is 22,000 bytes in size.1. BACKGROUND OF THE INVENTION[0004]Approximately one million people are diagnos...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/47A61K31/495A61K38/17
CPCC07K14/4705A61K31/495A61K38/1709A61K38/00A61P35/00
Inventor GREENE, LLOYD A.ANGELASTRO, JAMES
Owner RGT UNIV OF CALIFORNIA