The University of Texas System

Geron Corporation

Other

University of California

Geron Corporation & Board of Regents

Jerry W Shay

Woodring E Wright

Michael D West

Calvin B Harley

Elizabeth H Blackburn

Sergei M Gryaznov

Scott L Weinrich

Michael J McEachern

David R Corey

Nam Woo Kim

Mieczyslaw A Piatyszek

Wentian Wang

Homayoun Vaziri

James C Norton

Catherine M Strahl

Jef K De Brabander

Ilgen Mender

Nam Hoon Kim

Jef K DeBrabander

Yang-Xin Fu

Deepak Nijhawan

Pano Theodoropoulos

Tsung-Po Lai

James C Norton, Jr

Anli Zhang

Kimberly Batten

Jef DeBrabander

Jef Debrabander

Disclosed herein are methods of treatments with a telomerase-mediated telomere-targeting drug, 6-thio-2'-deoxyguanosine (6-thio-dG), checkpoint inhibitors and/or radiation therapy for treating cancers. Leads to tumor regression in innate and adaptive immune-dependent manners in syngeneic and humanized mouse cancer models.

Sequential treatment of cancers using 6-thio-dG, checkpoint inhibitors and radiation therapy

The described invention is directed toward pharmaceutical compositions and methods of using 6-mercaptopurine ribosides and analogues thereof for the treatment of cancer and other hyperproliferative diseases. The described compounds can be converted into telomere substrates in vivo and can be recognized by telomerase for incorporation into telomeres of telomerase active cells, leading to induction of cell death of the telomerase active cells.

Treatment of drug resistant proliferative diseases with telomerase mediated telomere altering compounds

The present disclosure encompasses methods and compositions for analyzing telomeres of genomic DNA, including the length of one or more telomeres. In specific embodiments, methods and compositions are employed for identification of the length of the shortest telomere in a collection of genomic DNA. In particular cases, the method greatly suppresses amplification of intra-genomic DNA fragments in comparison to telomeres by hindering their amplification using particular adaptors.

Method to measure the shortest telomeres

The described invention provides small molecule anti-cancer compounds that selectively target and inhibit measurable biological activity of truncated APC proteins, an immortalized Human Colonic Epithelial Cell (HCEC) model, and pharmaceutical compositions comprising at least one of the small molecule anti-cancer compounds and a pharmaceutically acceptable carrier.

Therapeutics targeting truncated adenomatous polyposis coli (APC) proteins

Methods for treating a telomerase-expressing cell characterized by an over-activation of telomerase in a subject in need thereof comprising administering a pharmaceutical composition comprising a first amount of a 6-mercaptopurine analog, and a second amount of a telomerase inhibitor, wherein the first amount and the second amount together comprises an amount effective to reduce stability of telomere length and to induce cell death in the telomerase-expressing cell are provided. The methods can be used to treat patients with lung cancer, colon cancer, or cervical cancer.

Telomerase mediated telomere altering compounds

The described invention provides methods for targeting emopamil binding protein (EBP) with small molecules that induce an abnormal feedback response by lowering endogenous cholesterol biosynthesis.

Targeting emopamil binding protein (EBP) with small molecules that induce an abnormal feedback response by lowering endogenous cholesterol biosynthesis

Compounds of the form O-(x-L)n, where O is an oligonucleoside having at least a plurality of N3'&#x2192;P5&#x2032; thiophosphoramidate (NPS) internucleoside linkages, a conjugated lipid moiety L, and at least one G-rich sequence motif as described, are effective to morphologically alter and reduce adhesion of cancer cells.

Compounds having anti-adhesive effects on cancer cells

Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to increase or decrease telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity and means are shown for slowing or reversing the loss of telomeric repeats in aging cells.

Diagnostic methods for conditions associated with elevated cellular levels of telomerase activity

Methods and kits are provided for diagnosis of specific cancerous conditions. The invention features a method for diagnosis of a condition in a patient associated with an elevated level of telomerase activity within a cell. The method involves determining the presence or amount of telomerase within the cells in the patient, e.g. by the use of the polymerase chain reaction. In one embodiment of the invention, the condition associated with elevated telomerase activity is chosen from prostate cancer, breast cancer, colon cancer, renal cancer, ovarian/cervical cancer, lung cancer, and leukemia. The invention allows cancer to be detected even in tissues and cells which are not positive by pathology.

Detecting cancerous conditions by assaying for telomerase activity

Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity and means are shown for slowing the loss of telomeric repeats in aging cells.

Screening methods to identify inhibitors of telomerase activity

The invention relates to peptide nucleic acids that inhibit telomerase activity in mammalian cells.

Inhibition of mammalian telomerase by peptide nucleic acids

A method of extracting telomerase from a cell sample having telomerase is provided which includes the step of contacting a cell sample with a buffer having (i) a non-ionic detergent at a concentration of not more than 5% (v/v) and (ii) an ionic detergent at a concentration of not more than 1 mM, to form a cell lysate. The method provides efficient extraction of telomerase that can be assayed for diagnostic and prognostic purposes.

Telomerase extraction method

Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity.

Growing community of inventors

Dallas, TX, United States of America

Jerry W Shay