University of Virginia Patent Foundation

Thermo Finnigan LLC

The University of Birmingham

The University of Oklahoma

Agenus Inc.

Johns Hopkins University

Albert Einstein College of Medicine

University Technologies International, Inc.

Craig L. Slingluff

Donald F. Hunt

David Kittlesen

Jeffrey Shabanowitz

Andrea L. Cox

Victor H. Engelhard

Jonathan Skipper

Donald F Hunt

Victor H Engelhard

Mark Cobbold

John Edward Philip Syka

Craig L Slingluff, Jr

Kara L Cummings

Rebecca C Obeng

Angela Lee Zarling

Stacy Alyse Malaker

William H Hilderbrand

Andrew Norris

Dina L Bai

Oriana E Hawkins

Andrea L Cox

Ann Michelle English

Ann M English

Scott A Ugrin

Suzanne L Topalian

George C Stafford, Jr

Christopher Mullen

Lee Earley

Philip D Compton

Teresa P DiLorenzo

Scott M Lieberman

Angela L Ambakhutwala

Jie Qian

Victor M Engelhard

Jennifer G Abelin

Sarah Amy Penny

Anne M Evans

Stanley G Nathenson

Pere Santamaria

Ronald C Hendrikson

Florence A Depontieu

Craig L Slingluff

Scott A Urgin

The present disclosure relates to novel and improved methods of analyzing proteins, peptides and polypeptides by mass spectrometry using ion-ion reactions. More specifically the disclosure relates to improved methods for implementing the m/z selective arresting of ion-ion reactions within the ion-ion reaction cell of a mass spectrometer system during a period where ion-ion reactions are performed.

Rapid identification and sequence analysis of intact proteins in complex mixtures

A set of target peptides are presented by HLA A*0101, A*0201, A*0301, B*4402, B*2705, B*1402, and B*0702 on the surface of disease cells. They are envisioned to among other things (a) stimulate an immune response to the proliferative disease, e.g., cancer, (b) to function as immunotherapeutics in adoptive T cell therapy or as a vaccine, (c) facilitate antibody recognition of tumor boundaries in surgical pathology samples, (d) act as biomarkers for early detection and/or diagnosis of the disease, and (e) act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex.

Target peptides for immunotherapy and diagnostics

The present invention describes novel tumor-specific phosphorylated peptides, nucleic acids encoding those peptides, and antibodies generated against said peptides. The genes, peptides, and antibodies described herein may be used as diagnostic indicators of the presence of breast cancer and/or used in therapeutics to treat breast cancer.

Identification of MHC class I phospho-peptide antigens from breast cancer utilizing SHLA technology and complementary enrichment strategies

A set of target peptides are presented by HLA A*0201, B*0301, B*0702 and B*2705 on the surface of disease cells. They are envisioned to, among other things, stimulate an immune response to the proliferative disease, e.g., colorectal cancer, to function as immunotherapeutics in adoptive T cell therapy or as a vaccine, facilitate antibody recognition of tumor boundaries in surgical pathology samples, act as biomarkers for early detection and/or diagnosis of the disease, and/or act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex.

Target peptides for colorectal cancer therapy and diagnostics

We characterized a total of 175 HLA-DR-associated phosphopeptides using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing and comparative analysis. Many were derived from source proteins which may have roles in cancer development, growth and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome 'fingerprints'. We generated HLA-DR&#x3b2;1*0101-restricted CD4T cells specific for a phospho-MART-1 peptide identified in two melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen presenting cells as well as for intact melanoma cells. MHC II-restricted phosphopeptides recognizable by human CD4T cells are potential targets for cancer immunotherapy.

Phosphopeptides as melanoma vaccines

The present invention is based on the identification of a predominant ligand of CD8T cells that are responsible for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN(A/I/L/V)FL (SEQ ID NO:3), FLWSVFWLI (SEQ ID NO:4), (T/A)YY(G/T)FLNFM (SEQ ID NO:5), LR(L/V)(F/L)(G/N)IDLL (SEQ ID NO:6), KWCANPDWI (SEQ ID NO:7), and SFCKSASIP (SEQ ID NO:8). Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8T cell that is cytotoxic to pancreatic islet &#x3b2;-cells from destroying a mammalian &#x3b2;-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.

Antigens targeted by prevalent pathogennic T cells in type 1 diabetes and uses thereof

A front-end reagent ion source for a mass spectrometer is disclosed. Reagent vapor is supplied to a reagent ionization volume located within a chamber of the mass spectrometer and maintained at a low vacuum pressure. Reagent ions are formed by interaction of the reagent vapor molecules with an electrical discharge (e.g., a glow discharge) within the ionization volume, and pass into the chamber of the mass spectrometer. At least one ion optical element located along the analyte ion path transports the reagent ions to successive chambers of the mass spectrometer. The reagent ions may be combined with the analyte ions to perform ion-ion studies such as electron transfer dissociation (ETD).

Method and apparatus for generation of reagent ions in a mass spectrometer

Melanoma-specific, A1- and A3-restricted CTL epitopes have been identified in tyrosinase and pMel-17, respectively, and may be used in the design of vaccines.

Peptides recognized by melanoma-specific A1-, A2- and A3-restricted cytoxic lymphocytes, and uses therefor

The instant disclosure identifies and synthesizes peptide residues initially isolated from a melanoma cell line. The peptides are capable of reconstituting an epitope recognized by tumor specific CTL. Some of the sequences are homologous with proteins identified as pMEL17, tyrosinase and cofilin. The present invention provides for the treatment of melanoma patients using synthetic peptides that reconstitute epitopes for melanoma specific CTL. In another embodiment the peptides are used as vaccines for imparting immunity. Alternatively, in one embodiment the peptides may be used to bind to antigen presenting cells in a method for providing specific antigenic stimulation of CTL. The instant invention provides CTL cell lines capable of recognizing reconstituted HLA-A2.1 epitopes and their use in methods of adoptive immunotherapy. The invention additionally provides for genes encoding for peptides capable of reconstituting epitopes recognized by tumor specific CTL and their use as vaccines in the prevention and management of melanoma. A splitter is also disclosed to identify active peptides.

Peptides recognized by melanoma-specific cytotoxic lymphocytes, and uses therefor

An apparatus for ionizing and vaporizing non-volatile or thermally labile molecules of a sample for introduction into a mass spectrometer analyzer which comprises a housing containing an ionization chamber; an ion exit port for the introduction of gaseous ions from said ionization chamber into a mass spectrometer analyzer on the portion of the housing attached to said mass spectrometer analyzer; inlet means for introducing a gaseous reactant into said ionization chamber within said housing; inlet means for admitting high energy radiation into said ionization chamber within said housing to at least partially ionize the molecules of said gaseous reactant; aperture means open into said ionization chamber of said housing for admitting a conductive emitter characterized by having a conductive element of a highly irregular surface upon which is deposited said sample for analysis into said mass spectrometer analyzer; and a vacuum exit aperture in said housing by which the pressure within said ionization chamber can be reduced.

Apparatus for producing ions of thermally labile or nonvolatile solids

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Charlottesville, VA, United States of America

Jeffrey Shabanowitz