Georgetown University

Medstar Health Research Institute, Inc.

Medstar Research Institute, Inc.

Anton Wellstein

Stephen E Epstein

Mary Susan Burnett

J Yun Tso

Debra Chao

Kevin J McDonnell

Justinian R Ngaiza

Anna T Riegel

Ronald Reiter

Marcel O Schmidt

Boussad Souttou

Daniel Raulais

Marc Vigny

Narayan Shivapurkar

Stephan Zbinden

Frank Czubayko

The present invention provides methods of identifying neopeptides in abnormal cells, with the methods comprising sequencing long-read messenger RNA (mRNA) isolated from the abnormal cells, identifying splice variants that could be generated from the sequenced long-read mRNA, determining if the abnormal cells contain neopeptides that correlate with the identified splice variants. The methods may also comprise identifying at least one neoantigen on the neopeptides that are present in the abnormal cells.

Methods of identifying novel proteins and antigens in cancer cells

In certain aspects, the disclosure relates to methods of predicting recurrence of colorectal cancer by using a combination of microRNAs in the circulation, wherein the microRNAs are selected from the group consisting of miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596. In other aspects, the disclosure relates to methods of treating colorectal cancer by administering a therapeutic agent after determining an increased risk of recurrence.

Compositions and methods for identification of relapse risk and treatment in patients with colorectal cancer

The invention relates to methods of lowering blood glucose levels in a subject, with the methods comprising administering fibroblast growth factor binding protein 3 (FGFBP3) or a variant thereof to a subject in need of having lower glucose levels.

Treatments for lowering glucose levels using FGF binding protein 3

Described herein are homing polypeptides that home to atherosclerotic plaque(s) in mammals and nucleic acids that encode such polypeptides. Also described are methods for detecting and treating conditions or disorders associated with, or characterized, by elevated levels of homing polypeptides that home to atherosclerotic plaque and/or vulnerable plaque.

Polynucleotides that home to atherosclerotic plaque

Described herein are polypeptides that home to developing microvasculature, (also referred to as developing microvessels), such as newly developing microvasculature in mammals, particularly in humans, and to DNA that encodes such polypeptides. These polypeptides are referred to herein as developing microvasculature homing polypeptides. In a specific embodiment, the homing peptides are collateral vessel endothelia (CVE) homing polypeptides, which have been shown to home to collateral vessel endothelia after ischemia.

Genes and proteins that home to developing microvessels

The present invention is directed to a method of identifying tissue targeting domains. In particular, the invention relates to methods for identifying a polynucleotide encoding a targeting domain which directs tumor cell localization to secondary sites, to methods of utilizing the polynucleotide and corresponding polypeptide or fragments thereof and compositions comprising the same.

Method for identifying targeting domains and methods and compositions comprising the same

The present invention concerns antibodies that neutralize at least one biological activity of pleiotrophin. The antibodies can inhibit cancer cell growth and angiogenesis in vitro or in vivo. The present invention provides for methods of inhibiting cancer cell growth or angiogenesis in a subject comprising administering to said subject an effective amount of the antibodies described herein. The present invention also provides for methods of making the neutralizing antibodies described herein.

Anti-pleiotrophin antibodies and methods of use thereof

This invention relates to the discovery that pleiotrophin binds to and activates a pleiotrophin-receptor which is responsible for the events associated with pleiotrophin activity including tumorigenesis, cell proliferation, and cell invasion. By interfering with that association, the cascade of events associated with pleiotrophin activity can be prevented or reversed. Further, by evaluating the effect of different compounds and conditions on the interaction, new drugs and treatments can be identified for use in preventing certain cancers and growth and developmental disorders.

Antibodies that bind to pleiotrophin growth factor receptor

Pleiotrophin growth factor receptor for the treatment of proliferative, vascular and neurological disorders

This invention relates to the AIB1 protein as a coactivator that potentiates the transcriptional activity of nuclear hormone receptors. The gene is amplified in a subset of human breast cancers. One splice variant of AIB1 transcribes a mRNA that lacks the exon 3 sequence. &#x394;3-AIB1 mRNA encodes a 130 kDa protein that lacks the N-terminal basic helix-loop-helix and a portion of the PAS dimerization domain. This 130 kDa protein was detected in MCF-7 breast cancer cells at levels 5-10% of the full length protein, whereas in non transformed mammary epithelium lines the &#x394;3-AIB1 protein is present at significantly lower levels compared to the full length AIB1. The abundance of &#x394;3-AIB1 mRNA is increased in human breast cancer specimens relative to that in normal breast tissue. Functional reporter gene assays revealed that the ability of &#x394;3-AIB1 to promote transcription mediated by the estrogen or progesterone receptors was significantly greater than that of the full-length protein. The &#x394;3-AIB1 isoform was also more effective than AIB1 in promoting transcription induced by epidermal growth factor. Thus, over expression of &#x394;3-AIB1 plays an important role in sensitizing breast tumor cells to hormone or growth factor stimulation.

Coactivators in the diagnosis and treatment of breast cancer

The invention relates to a novel method and kit for detecting and measuring pleiotrophin in samples and diagnosing pleiotrophin-positive diseases. The method involves incubating a sample suspected of containing PTN with anti-PTN antibodies and determining the presence of PTN using a sandwich ELISA. Also methods for treating a pleiotrophin-positive disease by administering an anti-PTN antibody or fragment thereof are provided.

Detection of pleiotrophin

Increased expression of a secreted FGF-binding protein (FGF-BP) occurs in certain autoimmune and malignant disease conditions. It is found, for example, that tumor secretions of FGF-BP results in mobilization and activation of locally-stored FGFs that can serve as an angiogenic switch molecule. Furthermore, it has been found that in an animal model of multiple sclerosis (MS), the exacerbation of the disease is accompanied by increased FGF-BP. Using ribozymes, it is possible to cause cleavage of the FGF-BP mRNA. Hence, administration of ribozymes which cleave the FGF-BP mRNA in sufficient amounts to inhibit disease processes triggered by FGF-BP is appropriate.

Inhibition of an FGF-binding protein using ribozymes

A fibroblast growth factor receptor-blocking peptide is provided. In one embodiment, the peptide is a retro-peptide of the fibroblast growth factor receptor. The receptor-blocking peptide may be used in a therapeutic method for treatment of viral diseases, hypervascular diseases, and tumors.

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Washington, DC, United States of America

Anton Wellstein