Abstract: PAGE-4 is a gene preferentially expressed in normal male and female reproductive tissues, prostate, testis, fallopian tube, uterus and placenta, as well as in prostate cancer, testicular cancer and uterine cancer. This expression pattern makes it a target for diagnosis and for vaccine based therapy of neoplasms of prostate, testis and uterus. The invention provides immunogenic compositions comprising PAGE-4 protein or immunogenic peptides thereof, methods of inhibiting the growth of malignant cells expressing PAGE-4, and methods of inducing an enhanced immune response to PAGE-4-expressing cancers.

Abstract: A polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Splice Variant-Novel Gene Expressed in Prostate (SV-NGEP). Polynucleotides encoding SV-NGEP are also disclosed, as are vectors including these poynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies and immunoconjugages are disclosed that specifically bind SV-NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds SV-NGEP, or a polynucleotide encoding SV-NGEP. Assays are disclosed for the detection of prostate cancer. Pharmaceutical compositions including an SV-NGEP polypeptide, an antibody that specifically binds SV-NEGP, or a polynucleotide encoding SV-NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.

Abstract: This invention provides nucleic acids containing sequences from a TCR? transcript from prostate epithelial cells and many breast cancer cells and a T-cell receptor gamma Alternate Reading frame Protein (“TARP”) expressed from the translation of those sequences. Vaccines made from TARP are useful in raising immune responses to cells in which the protein is expressed, including prostate cancer cells and cells of many breast cancers. The invention also provides methods for diagnosing the presence of prostate cancer and TARP-expressing breast cancers, as well as methods of administering TARP and nucleic acids encoding TARP to subjects.

Abstract: A polypeptide is disclosed that is detected in the breast cancer cells termed 68h05. Polynucleotides encoding 68h05 are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies and immunoconjugates are disclosed that specifically bind 68h05. Methods are disclosed for using a 68h05 polypeptide, an antibody that specifically binds 68h05, or a polynucleotide encoding 68h05, such as in the treatment of breast cancer or prostate cancer. Assays are disclosed for the detection breast or prostate cancer. Pharmaceutical compositions including a 68h05 polypeptide, an antibody that specifically binds 68h05, or a polynucleotide encoding 68h05 are also disclosed. These pharmaceutical compositions are of use in the treatment of breast or prostate cancer.

Abstract: A new polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Novel Gene Expressed in Prostate (NGEP). Polynucleotides encoding NGEP are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies are disclosed that specifically bind NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP. Assays are disclosed for the detection prostate cancer. Pharmaceutical compositions including an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.

Abstract: The invention provides recombinant immunotoxins that have been modified from a parental immunotoxin to lower liver toxicity. The immunotoxins are created by specifically mutating charged residues in the framework regions of the heavy chain, the light chain, or both, of the antibody portion or antigen-binding fragment thereof of the parental immunotoxin to reduce the pI of the antibody or fragment. In preferred forms, the antibody portion of the parental is an anti-Tac, anti-mesothelin, or anti-LewisY antigen antibody or antigen-binding fragment, and in particularly preferred forms the antibody portion is an M16 dsFv, a St6 dsFv or a Mt9 dsFv, or a sequence that has at least 90% sequence identity to one of these molecules but retain the particular mutations that lower pI without affecting antibody activity. The invention further provides nucleic acids encoding the recombinant immunotoxins of the invention, expression cassettes comprising the nucleic acids, and host cells comprising the expression cassettes.

Abstract: The invention relates to the surprising discovery that XAGE-1 is translated as two proteins, a 9 kD protein, termed p9, and a 16.3 kD protein, termed p16. The invention further relates to the surprising discovery that XAGE-1 is expressed in a number of important human cancers, specifically: prostate cancer, lung cancer, ovarian cancer, breast cancer, glioblastoma, pancreatic cancer, T cell lymphoma, melanoma, and histocytic lymphoma. The proteins p9 and p16, immunogenic fragments thereof, analogs of these proteins, and nucleic acids encoding these proteins, fragments, or analogs, can be administered to persons with XAGE-1 expressing cancers to raise or augment an immune response to the cancer. The invention further provides nucleic add sequences encoding the proteins, as well as expression vectors, host cells, and antibodies to the proteins. Further, the invention provides immunoconjugates that comprise an antibody to p16 or to p9, and an effector molecule, such as a label, a radioisotope, or a toxin.

Abstract: The present invention is directed to the site-specific PEGylation of immunoconjugates. In particular, the present invention provides immunoconjugates wherein a connector molecule attaching a targeting molecule to an effector molecule is conjugated to one or more polyethylene glycol molecules. The present invention further provides methods for increasing the antitumor activity of an immunotoxin, comprising attaching in a site-specific manner one or more polyethylene glycol molecules to a linker connecting a toxic moiety to a targeting moiety of an immunotoxin.

Abstract: The present invention relates to disulfide-stabilized recombinant polypeptide molecules which have the binding ability and specificity for another peptide, such as the variable region of an antibody molecule. Methods of producing these molecules and nucleic acid sequences encoding these molecules are also described. In particular, the invention discloses Fv antibody fragments stabilized by a disulfide bond connecting the VH and VL regions of the Fv fragment. The &agr; and &bgr; chains of T cell receptors may be similarly stabilized by means described in the invention.

Abstract: The invention provides methods for inhibiting the growth of a cell bearing a LewisY antigen. The methods involve contacting the cell with a composition comprising an Fv region of a light chain of a monoclonal antibody selected from B1, B3, and B5, and the Fv region of a humanized heavy chain of a monoclonal antibody independently selected from B1, B3, and B5, provided that if the heavy and the light chains are from the same antibody, the residue at position 95 of the heavy chain is a serine, and, if the antibody chain is from B3, the residue at position 4 of the light chain can be a leucine and the residue at position 82b of the heavy chain can be an arginine. The Fv regions are joined to an effector molecule selected from a chemotherapeutic agent, a toxin, a radioisotope, and a liposome loaded with a chemotherapeutic agent. In preferred embodiments, the heavy chain and the light chain are recombinantly fused, and the Fv regions are recombinantly fused to a toxin.

Abstract: The present invention relates to disulfide-stabilized recombinant polypeptide molecules which have the binding ability and specificity for another peptide, such as the variable region of an antibody molecule. Methods of producing these molecules and nucleic acid sequences encoding these molecules are also described. In particular, the invention discloses Fv antibody fragments stabilized by a disulfide bond connecting the V.sub.H and V.sub.L regions of the Fv fragment. The .alpha. and .beta. chains of T cell receptors may be similarly stabilized by means described in the invention.

Abstract: This invention provides for recombinant single chain antibodies capable of specifically binding to a Lewis.sup.Y -related carbohydrate antigen and fusion proteins comprising these antibodies. More particularly, the invention provides for humanized chain Fv regions of the monoclonal antibodies B1, B3 and B5 and fusion proteins incorporating these humanized antibodies. The antibodies may comprise humanized variable heavy (V.sub.H) chains, humanized variable light (V.sub.L) chains, or both. The invention also provides for DNA sequences encoding the various humanized antibodies. In addition, the invention provides for methods of detecting cells bearing a Lewis.sup.Y antigen in a patient and for methods of killing or inhibiting the growth of cells bearing a Lewis.sup.Y antigen in a patient.

Abstract: The present invention relates to disulfide-stabilized recombinant polypeptide molecules which have the binding ability and specificity for another peptide, such as the variable region of an antibody molecule. Methods of producing these molecules and nucleic acid sequences encoding these molecules are also described. In particular, the invention discloses Fv antibody fragments stabilized by a disulfide bond connecting the V.sub.H and V.sub.L regions of the Fv fragment. The .alpha. and .beta. chains of T cell receptors may be similarly stabilized by means described in the invention.