University of Virginia Patent Foundation

Rijksuniversiteit Te Leiden

The University of Birmingham

Johns Hopkins University

Rijsuniversiteit Te Leiden

Victor H Engelhard

Donald F Hunt

Jeffrey Shabanowitz

Kara L Cummings

Rebecca C Obeng

Els A J M Goulmy

Craig L Slingluff, Jr

Angela Lee Zarling

Mark Cobbold

Stacy Alyse Malaker

Angela L Ambakhutwala

David Kittlesen

Joel M Linden

Suzanne L Topalian

Andrea L Cox

Jonathan Skipper

Florence A Depontieu

Ronald C Hendrikson

Jie Qian

Els A Goulmy

Courtney M Lappas

Angela Zarling

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

Provided are isolated TCRs, TCR-like molecules, and portions thereof that bind to phosphopeptide-HLA-A2 complexes. The isolated TCRs, TCR-like molecules, or portions are optionally soluble TCRs, TCR-like molecules, or portions. Also provided are isolated nucleic acids encoding the disclosed TCRs, TCR-like molecules, or portions; host cells that contain the disclosed TCRs, TCR-like molecules, or portions; pharmaceutical compositions that include the disclosed TCRs, TCR-like molecules, portions, nucleic acids, and/or T cells; kits; and methods of using the same.

Isolated T cell receptors and methods of use therefor

The present invention encompasses novel peptides useful for preventing and treating cancer, particularly melanoma. Multiple sequences of interest are provided and these sequences have been incorporated into other peptides to obtain a series of peptides of about 30 amino acid residues in length wherein the properties of each combine to yield an effective cocktail for treating melanoma, which surpasses the use of single peptides as immunogens, as well as shorter peptides as immunogens.

Composition and methods for treating melanoma

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 relates to a method for treating recurrent tumor metastases following liver resection that includes administration of an effective amount of an agonist of Aadenosine receptors (ARs).

Method of treating ischemia reperfusion injury by inhibiting NKT cell activity

A peptide sequence of the so-called minor H antigen. The minor H antigens are associated with Graft versus Host disease. The peptide and its derivatives find many uses in bone marrow transplantation, organ transplantation, and in the treatment of leukemia. The peptide and its derivatives can be incorporated into vaccines and pharmaceutical formulations, and they can be used in diagnostic test kits. The peptide is derived from the HA-1 minor antigen, and has the sequence VLXDDLLEA (SEQ ID NO: 1), wherein X represents a histidine or arginine residue. Both donors and recipients in bone marrow transplantation can be treated with the peptides, optionally in combination with other peptides, coupled to carriers, and with suitable excipients and/or adjuvants.

HA-1 antigen

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 present invention relates to a peptide which is immunologically recognizable as a T cell epitope of the minor Histocompatibility antigen H-Y. The peptide comprises amino acid sequence SPSVDKARAEL (SEQ ID NO: 1) or FIDSYICQV (SEQ ID NO: 2). The peptide is obtainable from the minor Histocompatibility antigen H-Y. Providing a toxic moiety to the peptide eliminates T cells having specific binding affinity for the peptide. The peptide induces tolerance for transplantations when administered to H-Y-negative recipients.

H-Y antigen

A peptide sequence of the so-called minor H antigen. The minor H antigens are associated with Graft versus Host disease. The peptide and its derivatives find many uses in bone marrow transplantation, organ transplantation, and in the treatment of leukemia. The peptide and its derivatives can be incorporated into vaccines and pharmaceutical formulations, and they can be used in diagnostic test kits. The peptide is derived from the HA-1 minor antigen, and has the sequence VLXDDLLEA (SEQ. I.D. NO. 1), wherein X represents a histidine or arginine residue. Both donors and recipients in bone marrow transplantation can be treated with the peptides, optionally in combination with other peptides, coupled to carriers, and with suitable excipients and/or adjuvants.

Cysteine-depleted CTL epitopes can elicit a stronger or more specific CTL response than the native, cysteine-containing CTL epitope of a disease associated antigen.

Cysteine-depleted peptides recognized by A3-restricted cytotoxic lymphocytes, and uses therefor

The present invention relates to a peptide which is immunologically recognizable as a T cell epitope of the minor histocompatibility antigen H-Y. The peptide comprises amino acid sequence SPSVDKARAEL (SEQ ID NO:1), or FIDSYICQV (SEQ ID NO:2). The peptide is obtainable from the minor histocompatibility antigen H-Y. Providing a toxic moiety to the peptide eliminates T Cells having specific binding affinity for the peptide. The peptide induces tolerance for transplantations when administered to H-Y-negative recipients.

The present invention discloses the first peptide sequence of a so called minor H antigen, The minor H antigens are associated with the Graft-versus-Host Disease. The peptide and its derivatives find many uses in bone marrow transplantation, organ transplantation and in the treatment of leukemia. The peptide and its derivatives can be incorporated in vaccines, in pharmaceutical formulations and they can be used in diagnostic test kits. The peptide is derived from the HA-2 minor antigen and has the sequence YXGEVXVSV (SEQ ID NO: 1), wherein X represents a leucine or an isoleucine residue. Both donors and recipients in bone marrow transplantation can be treated with the peptides, optionally in combination with other peptides, coupled to carriers, with suitable excipients and/or adjuvants.

Growing community of inventors

Crozet, VA, United States of America

Victor H Engelhard