Abstract: This invention relates generally to antibody-drug conjugates (ADCs). In particular, the invention relates to ADCs which comprise an antibody or antigen-binding fragment thereof which binds to prostate-specific membrane antigen (PSMA) and is conjugated to monomethylauristatin norephedrine or monomethylauristatin phenylalanine. The antibody-drug conjugate has a PC-3™ cell to C4-2 or LNCaP™ cell selectivity of at least 250. The invention also relates, in part, to compositions of and methods of using the ADCs. The methods provided include, for example, methods for treating a PSMA-mediated disease.

Abstract: This invention provides a method of reducing viral load in an HIV-1-infected human subject which comprises administering to the subject an effective HIV-1 viral load reducing dose of a CCR5 receptor antagonist, such as a humanized antibody designated PRO 140 or an anti-CCR5 receptor monoclonal antibody, wherein the viral load reducing dose achieves an average maximum decrease of viral load in the subject of at least 1.83 log10 to 2.5 log10 at about ten days following administration of the CCR5 receptor antagonist and wherein the viral load reducing dose further achieves a mean viral load reduction of 1.7 log10 at about nine days following administration of the CCR5 receptor antagonist. The viral load reducing dose results in a suppression of mean viral load by 1.0 log10 within about four days following administration of the CCR5 receptor antagonist, and suppression of viral load in the subject persists at or below a level of reduction of 1.0 log10 for about two to three weeks.

Abstract: This invention provides a method of reducing viral load in an HIV-1-infected human subject which comprises administering to the subject an effective HIV-1 viral load reducing dose of a CCR5 receptor antagonist, such as a humanized antibody designated PRO 140 or an anti-CCR5 receptor monoclonal antibody, wherein the viral load reducing dose achieves an average maximum decrease of viral load in the subject of at least 1.83 log10 to 2.5 log10 at about ten days following administration of the CCR5 receptor antagonist and wherein the viral load reducing dose further achieves a mean viral load reduction of 1.7 log10 at about nine days following administration of the CCR5 receptor antagonist.

Abstract: The invention includes stable multimeric, particularly dimeric, forms of PSMA protein, compositions and kits containing dimeric PSMA protein as well as methods of producing, purifying and using these compositions. Such methods include methods for eliciting or enhancing an immune response to cells expressing PSMA, including methods of producing antibodies to dimeric PSMA, as well as methods of treating cancer, such as prostate cancer.

Abstract: The present invention provides antibodies that bind to prolactin receptor (PRLR) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PRLR with high affinity. In certain embodiments, the invention includes antibodies that bind PRLR and block prolactin-mediated cell signaling. In other embodiments, the invention includes antibodies that bind PRLR but do not block prolactin-mediated cell signaling. According to certain embodiments, the invention includes antibodies that bind to the first fibronectin-like type III domain of the extracellular domain of PRLR. The antibodies of the invention may be fully human antibodies. The invention includes anti-PRLR antibodies conjugated to a cytotoxic agent, radionuclide, or other moiety detrimental to cell growth or proliferation. The antibodies of the invention are useful for the treatment of various cancers as well as other PRLR-related disorders.

Abstract: Methods of killing prostate-specific membrane antigen (PSMA)-expressing, taxane-resistant cancer cells are provided. In particular, PSMA-expressing, taxane-resistant cancer cells are contacted with an antibody-drug conjugate (ADC) that comprises an antibody or antigen-binding fragment thereof that specifically binds to PSMA conjugated to monomethylauristatin norephedrine or monomethylauristatin phenylalanine.

Abstract: The invention includes stable multimeric, particularly dimeric, forms of PSMA protein, compositions and kits containing dimeric PSMA protein as well as methods of producing, purifying and using these compositions. Such methods include methods for eliciting or enhancing an immune response to cells expressing PSMA, including methods of producing antibodies to dimeric PSMA, as well as methods of treating cancer, such as prostate cancer.

Abstract: Provided herein are reagents, compositions, and therapies with which to treat Clostridium difficile infection and related disease conditions and pathologies, such as Clostridium difficile-associated diarrhea, resulting from infection by Clostridium difficile bacteria and the enterotoxins produced by these bacteria. In particular, antibodies or antigen-binding fragments thereof that bind specifically to toxin A and/or toxin B of C difficile and neutralize the activities of these toxins; compositions comprising such antibodies; and methods of using the antibodies and the compositions are provided.

Abstract: Provided herein are a number of methods, assays and diagnostic tests based on one or more biomarkers as well as related kits and compositions that can be used to identify subjects or patients that would likely benefit from a treatment (or continued treatment), such as a PSMA targeted therapy. Also provided are methods for treating the identified subjects or patients.

Abstract: Compositions and methods related to inhibiting the proliferation of or killing of prostate-specific membrane antigen (PSMA)-expressing cells are provided herein. In some embodiments, PSMA-expressing cells are contacted with (i) a compound that increases cell surface expression of PSMA and (ii) a PSMA ligand conjugate. In other embodiments, the PSMA-expressing cells are contacted with (i) prednisone and (ii) a PSMA ligand conjugate. In some of these embodiment ts, the PSMA-expressing cells are further contacted with (iii) a compound that increases cell surface expression of PSMA.

Abstract: Provided herein are reagents, compositions, and therapies with which to treat Clostridium difficile infection and related disease conditions and pathologies, such as Clostridium difficile-associated diarrhea, resulting from infection by Clostridium difficile bacteria and the enterotoxins produced by these bacteria. In particular, antibodies or antigen-binding fragments thereof that bind specifically to toxin A and/or toxin B of C difficile and neutralize the activities of these toxins; compositions comprising such antibodies; and methods of using the antibodies and the compositions are provided.

Abstract: The present invention provides antibodies that bind to prolactin receptor (PRLR) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PRLR with high affinity. In certain embodiments, the invention includes antibodies that bind PRLR and block prolactin-mediated cell signaling. In other embodiments, the invention includes antibodies that bind PRLR but do not block prolactin-mediated cell signaling. According to certain embodiments, the invention includes antibodies that bind to the first fibronectin-like type III domain of the extracellular domain of PRLR. The antibodies of the invention may be fully human antibodies. The invention includes anti-PRLR antibodies conjugated to a cytotoxic agent, radionuclide, or other moiety detrimental to cell growth or proliferation. The antibodies of the invention are useful for the treatment of various cancers as well as other PRLR-related disorders.

Abstract: This method provides a method for reducing HIV-1 viral load in an HIV-1-infected human subject which comprises administering to the subject at a predefined interval effective HIV-1 viral load-reducing doses of (a) a humanized antibody designated PRO 140, or of (b) an anti-CCR5 receptor monoclonal antibody. This invention also provides a method for inhibiting in a human subject the onset or progression of an HIV-1-associated disorder, the inhibition of which is effected by inhibiting fusion of HIV-1 to CCR5+CD4+ target cells in the subject. This invention also provides a method for treating a subject infected with HIV-1 comprising administering to the subject (a) a monoclonal antibody which (i) binds to a CCR5 receptor on the surface of the subject's CD4+ cells and (ii) inhibits fusion of HIV-1 to the subject's CCR5+CD4+ cells, and (b) a non-antibody CCR5 receptor antagonist, in amounts effective to treat the subject.

Abstract: The invention includes stable multimeric, particularly dimeric, forms of PSMA protein, compositions and kits containing dimeric PSMA protein as well as methods of producing, purifying and using these compositions. Such methods include methods for eliciting or enhancing an immune response to cells expressing PSMA, including methods of producing antibodies to dimeric PSMA, as well as methods of treating cancer, such as prostate cancer.

Abstract: This method provides a method for reducing HIV-1 viral load in an HIV-1-infected human subject which comprises administering to the subject at a predefined interval effective HIV-1 viral load-reducing doses of (a) a humanized antibody designated PRO 140, or of (b) an anti-CCR5 receptor monoclonal antibody. This invention also provides a method for inhibiting in a human subject the onset or progression of an HIV-1-associated disorder, the inhibition of which is effected by inhibiting fusion of HIV-1 to CCR5+CD4+ target cells in the subject. This invention also provides a method for treating a subject infected with HIV-1 comprising administering to the subject (a) a monoclonal antibody which (i) binds to a CCR5 receptor on the surface of the subject's CD4+ cells and (ii) inhibits fusion of HIV-1 to the subject's CCR5+CD4+ cells, and (b) a non-antibody CCR5 receptor antagonist, in amounts effective to treat the subject.

Abstract: This invention provides methods for inhibiting fusion of HIV-1 to CD4+ cells, comprising contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to CD4+ cells is inhibited. Also provided are methods for inhibiting HIV-1 infection of CD4+ cells, comprising contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to CD4+ cells is inhibited, thereby inhibiting the HIV-1 infection. This invention provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells and pharmaceutical compositions comprising an amount of the non-chemokine agent capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells effective to prevent fusion of HIV-1 to CD4+ cells and a pharmaceutically acceptable carrier.

Abstract: Provided herein are reagents, compositions, and therapies with which to treat Clostridium difficile infection and related disease conditions and pathologies, such as Clostridium difficile-associated diarrhea, resulting from infection by Clostridium difficile bacteria and the enterotoxins produced by these bacteria. In particular, antibodies or antigen-binding fragments thereof that bind specifically to toxin A and/or toxin B of C difficile and neutralize the activities of these toxins; compositions comprising such antibodies; and methods of using the antibodies and the compositions are provided.

Abstract: The invention includes stable multimeric, particularly dimeric, forms of PSMA protein, compositions and kits containing dimeric PSMA protein as well as methods of producing, purifying and using these compositions. Such methods include methods for eliciting or enhancing an immune response to cells expressing PSMA, including methods of producing antibodies to dimeric PSMA, as well as methods of treating cancer, such as prostate cancer.

Abstract: The invention includes antibodies or antigen-binding fragments thereof which bind specifically to conformational epitopes on the extracellular domain of PSMA, compositions containing one or a combination of such antibodies or antigen-binding fragments thereof, hybridoma cell lines that produce the antibodies, and methods of using the antibodies or antigen-binding fragments thereof for cancer diagnosis and treatment. The invention also includes oligomeric forms of PSMA proteins, compositions comprising the multimers, and antibodies that selectively bind to the multimers.

Abstract: Methods of killing prostate-specific membrane antigen (PSMA)-expressing, taxane-resistant cancer cells are provided. In particular, PSMA-expressing, taxane-resistant cancer cells are contacted with an antibody-drug conjugate (ADC) that comprises an antibody or antigen-binding fragment thereof that specifically binds to PSMA conjugated to monomethylauristatin norephedrine or monomethylauristatin phenylalanine.