Agensys, Inc.

University of California

Genentech, Inc.

Urogenesys, Inc.

Douglas C Saffran

Arthur B Raitano

Rene S Hubert

Daniel E Afar

Kahan Leong

Aya Jakobovits

Stephen Chappell Mitchell

Daniel E H Afar

Mary Faris

Steven Chappell Mitchell

Owen N Witte

Pia M Challita-Eid

Robert E Reiter

Wangmao Ge

Robert Kendall Morrison

Steve Chappell Mitchell

Igor Vivanco

David J Rawlings

Satoshi Tsukada

Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed 'STEAP' (Six Transmembrane Epithelial Antigens of the Prostate). Four particular human STEAPs are described and characterized herein. The prototype member of the STEAP family, STEAP-1, appears to be a type IIIa membrane protein expressed predominantly in prostate cells in normal human tissues. Structurally, STEAP-1 is a 339 amino acid protein characterized by a molecular topology of six transmembrane domains and intracellular N- and C-termini, suggesting that it folds in a 'serpentine' manner into three extracellular and two intracellular loops. STEAP-1 protein expression is maintained at high levels across various stages of prostate cancer. Moreover, STEAP-1 is highly over-expressed in certain other human cancers.

Serpentine transmembrane antigens expressed in human cancers and uses thereof

A novel prostate tumor associated gene (designated 24P4C12) and its encoded protein is described. 24P4C12 is highly expressed in prostate tissue xenografts, providing evidence that it is turned on in at least some prostate cancers. 24P4C12 provides a diagnostic and/or therapeutic target for prostate and other cancers.

13-transmembrane protein expressed in prostate cancer

Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed 'STEAP' (Six Transmembrane Epithelial Antigen of the Prostate). Four particular human STEAPs are described and characterized herein. The human STEAPs exhibit a high degree of structural conservation among them but show no significant structural homology to any known human proteins. The prototype member of the STEAP family, STEAP-1, appears to be a type IIIa membrane protein expressed predominantly in prostate cells in normal human tissues. Structurally, STEAP-1 is a 339 amino acid protein characterized by a molecular topology of six transmembrane domains and intracellular N- and C-termini, suggesting that it folds in a 'serpentine' manner into three extracellular and two intracellular loops.

A novel gene (designated 101P3A11 or PHOR-1) and its encoded protein, and variants thereof, are described wherein 101P3A11 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 101P3A11 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 101P3A11 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 101P3A11 can be used in active or passive immunization.

Protein showing enhanced expression in cancer cells

Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed 'STEAP' (Six Transmembrane Epithelial Antigen of the Prostate). Four particular human STEAPs are described and characterized herein. The human STEAPs exhibit a high degree of structural conservation among them but show no significant structural homology to any known human proteins. The prototype member of the STEAP family, STEAP-1, appears to be a type IIIa membrane protein expressed predominantly in prostate cells in normal human tissues. Structurally, STEAP-1 is a 339 amino acid protein characterized by a molecular topology of six transmembrane domains and intracellular N- and C-termini, suggesting that it folds in a 'serpentine' manner into three extracellular and two intracellular loops. STEAP-1 protein expression is maintained at high levels across various stages of prostate cancer. Moreover, STEAP-1 is highly over-expressed in certain other human cancers.

Serpentine transmembrane antigens expressed in human cancers and uses therefor

Described is a novel gene and its encoded secreted tumor antigen, termed BPC-1, and to diagnostic and therapeutic methods and compositions useful in the management of various cancers which express BPC-1, particularly including prostate cancer and bladder cancer. In human normal tissues, BPC-1 is only expressed in certain tissues of the brain. However, BPC-1 is expressed at high levels in prostate cancer cells and is also expressed in bladder cancer cells. The structure of BPC-1 includes a signal sequence and a CUB domain. BPC-1 protein is secreted. Preliminary experimental evidence suggests that BPC-1 is directly involved in oncogenesis or maintenance of the transformed phenotype of cancer cells expressing BPC-1. BPC-1 also appears to bind specifically to a cellular protein expressed in prostate cancer cells and other cells.

BPC-1: a secreted brain-specific protein expressed and secreted by prostate and bladder cancer cells

Compositions for the diagnosis and therapy of prostate and colon cancer, derived from or based on a novel prostate-specific, androgen-regulated, cell membrane associated and secreted serine protease termed 20P1F12/TMPRSS2 are described. A full length cDNA comprising the entire coding sequence of the 20P1F12/TMPRSS2 gene (also designated 20P1F12-GTC1 herein) is provided (FIG.). Among the compositions provided are antibodies that bind to 20P1F12/TMPRSS2 proteins and polypeptide fragments thereof, including antibodies labeled with a detectable marker or toxin or therapeutic composition. The invention also provides prognostic and diagnostic methods of examining a biological sample for evidence of disregulated cellular growth by comparing the status of 20P1F12/TMPRSS2 in the biological sample to the status of 20P1F12/TMPRSS2 in a corresponding normal sample, wherein alterations in the status of 20P1F12/TMPRSS2 in the biological sample are associated with disregulated cellular growth. The invention further provides various therapeutic compositions and strategies for treating prostate cancer, including particularly, 20P1F12/TMPRSS2 polypeptide and anti-20P1F12/TMPRSS2 antibody therapy methods and compositions, cancer vaccines, and small molecule therapy.

Methods to detect tumors using 20P1F12/TMPRSS2 expression

Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed 'STEAP' (Six Transmembrane Epithelial Antigen of the Prostate). Four particular human STEAPs are described and characterized herein. The human STEAPs exhibit a high'degree of structural conservation among them but show no significant structural homology to any known human proteins. STEAP-2 is a 454 amino acid protein characterized by a predicted molecular topology of six transmembrane domains and intracellular N- and C-termini, suggesting that it folds in a 'serpentine' manner into three extracellular and two intracellular loops.

Antibodies to protein expressed in prostate cancer

Described is a family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed 'STEAP' (ixransmembranepithelialntigen of therostate). Four particular human STEAPs are described and characterized herein. The human STEAPs exhibit a high degree of structural conservation among them but show no significant structural homology to any known human proteins. The prototype member of the STEAP family is STEAP-1, which appears to be a type IIIa membrane protein. STEAP-1 is a 339 amino acid protein. STEAP-1 protein expression is maintained at high levels across various stages of prostate cancer. Moreover, STEAP-1 is highly over-expressed in certain other human cancers.

Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed 'STRAP' Serpentine TRansmembrane Antigens of the Prostate). Four particular human STRAPs are described and characterized herein. The human STRAPs exhibit a high degree of structural conservation among them but show no significant structural homology to any known human proteins. The prototype member of the STRAP family, STRAP-1, appears to be a type IIIa membrane protein expressed predominantly in prostate cells in normal human tissues. Structurally, STRAP-1 is a 339 amino acid protein characterized by a molecular topology of six transmembrane domains and Intracellular N- and C-termini, suggesting that It folds In a 'serpentine' manner Into three extracellular and two intracellular loops. STRAP-1 protein expression is maintained at high levels across various stages of prostate cancer. Moreover, STRAP-1 is highly over-expressed In certain other human cancers.

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Los Angeles, CA, United States of America

Douglas C Saffran