Abstract: The present invention relates to a method for treating cancer. This method involves providing a first agent comprising a first targeting component coupled to a first cancer therapeutic component and providing a second agent comprising a second targeting component coupled to a second cancer therapeutic component. The first and second targeting components have different biodistributions and/or pharmacokinetics. The first and second agents are administered to a subject having cancer to treat the cancer. Also disclosed is a combination therapeutic comprising the first and second agents.

Abstract: The present application relates to a bi-functional therapeutic for treating cancer that includes a targeting component which targets a tumor-associated antigen and an enzyme which, when delivered to a tumor by said targeting component, converts the tumor phenotype to that of an incompatible allograft or xenograft. The enzyme is coupled to the targeting component. Also disclosed is a method for treating cancer comprising administering the bi-functional therapeutic.

Abstract: The present application relates to methods of treating a subject for cancer. The method involves providing a first agent comprising a first targeting component coupled to a first cancer therapeutic component and providing a second agent comprising a second targeting component coupled to a second cancer therapeutic component. The first and second targeting components have different biodistributions and/or pharmacokinetics in the subject. The first and second agents are administered no more than eight hours apart from each other, to the subject to treat cancer. As a result of the administering, the amount of first and second cancer therapeutic component internalized and retained within a tumor is greater than the sum of first and second cancer therapeutic component internalized and retained in a tumor if each of the first and second agents were administered alone. Also disclosed is a combination therapeutic comprising the first and second agents blended together.

Abstract: The present application relates to methods of treating and imaging cancer. The methods involve providing a first agent comprising a first targeting component coupled to a cancer therapeutic component or an imaging component and providing a second agent comprising a second targeting component alone, wherein the second targeting component increases the uptake, internalization, and/or retention of the first targeting component coupled to a cancer therapeutic component or imaging component. The first and second agents are then administered to a subject having cancer to treat cancer. Also disclosed is a combination therapeutic or a combination imaging system, each comprising the first and second agents.

Abstract: The present invention relates to a method for treating cancer. This method involves providing a first agent comprising a first targeting component coupled to a first cancer therapeutic component and providing a second agent comprising a second targeting component coupled to a second cancer therapeutic component. The first and second targeting components have different biodistributions and/or pharmacokinetics. The first and second agents are administered to a subject having cancer to treat the cancer. Also disclosed is a combination therapeutic comprising the first and second agents.

Abstract: The present invention relates to a method for treating cancer. This method involves providing a first agent comprising a first targeting component coupled to a first cancer therapeutic component and providing a second agent comprising a second targeting component coupled to a second cancer therapeutic component. The first and second targeting components have different biodistributions and/or pharmacokinetics. The first and second agents are administered to a subject having cancer to treat the cancer. Also disclosed is a combination therapeutic comprising the first and second agents.

Abstract: The present invention relates to a method for treating cancer. This method involves providing a first agent comprising a first targeting component coupled to a first cancer therapeutic component and providing a second agent comprising a second targeting component coupled to a second cancer therapeutic component. The first and second targeting components have different biodistributions and/or pharmacokinetics. The first and second agents are administered to a subject having cancer to treat the cancer. Also disclosed is a combination therapeutic comprising the first and second agents.

Abstract: The present invention relates to a method for treating cancer. This method involves providing a first agent comprising a first targeting component coupled to a first cancer therapeutic component and providing a second agent comprising a second targeting component coupled to a second cancer therapeutic component. The first and second targeting components have different biodistributions and/or pharmacokinetics. The first and second agents are administered to a subject having cancer to treat the cancer. Also disclosed is a combination therapeutic comprising the first and second agents.

Abstract: A method for identifying a patient for cancer therapy can include administering a diagnostic dose of a detectably labeled first binding agent to a patient, the detectably labeled binding agent being capable of binding a molecular target. The method also includes selecting a patient for administration of a therapeutic dose of a second binding agent capable of binding a cellular target, wherein the selected patient exhibits a positive reading for the detectably labeled first binding agent. Furthermore, the method can include administering a therapeutic dose of the second binding agent to the patient.

Abstract: Methods of treating cancer in a patient are provided. In some embodiments the method comprises administering an antibody that is capable of binding to the extracellular domain of PSMA after first adminstering a hormal therapy.

Abstract: Disclosed are methods of enhancing prostate cancer vulnerability to an anti-PSMA targeted therapy by administering an anti-androgen therapy to a subject so that the prostate cancer vulnerability in the subject is enhanced 2-4 weeks after the administration of the anti-androgen therapy and then administering to the subject an antibody or antigen binding fragment thereof that is capable of binding to the extracellular domain of PSMA after the prostate cancer vulnerability is enhanced. The anti-androgen therapy can be a hormonal therapy or surgical castration. The antibody or antigen binding fragment thereof may optionally be conjugated to a cytotoxic agent, e.g., Lutetium-177.

Abstract: Prostate cancer (PC) is an entity that encompasses different types of tumors, including adenocarcinomas and non-adenocarcinomas. Adenocarcinomas and non-adenocarcinomas respond to, and therefore should be treated, with different treatments. Even within the adenocarcinomas, the lethality of tumors is highly variable, from low risk/indolent/non-life threatening to high risk/lethal. The inability to accurately predict the behavior of a particular cancer makes treatment decisions difficult and highly inexact. Elevated expression of prostate specific membrane antigen (PSMA) expression is a molecular hallmark of lethal prostate adenocarcinoma. Assessment of PSMA expression levels to predict the behavior of a particular cancer will be useful in the diagnosis and treatment of PC.

Abstract: Modified antibodies, or antigen-binding fragments thereof, to the extracellular domain of human prostate specific membrane antigen (PSMA) are provided. The modified anti-PSMA antibodies, or antigen-binding fragments thereof, have been rendered less immunogenic compared to their unmodified counterparts to a given species, e.g., a human. Pharmaceutical compositions including the aforesaid antibodies, nucleic acids, recombinant expression vectors and host cells for making such antibodies and fragments are also disclosed. Methods of using the antibodies of the invention to detect human PSMA, or to ablate or kill a PSMA-expressing cell, e.g., a PSMA-expressing cancer or prostatic cell, either in vitro or in vivo, are also provided.

Abstract: Use of antibodies or binding portions thereof, probes, ligands, or other biological agents which either recognize an extracellular domain of prostate specific membrane antigen (PSMA) or bind to and are internalized with PSMA. These biological agents can be labeled and used for detection of cancerous tissues, particularly cancerous tissues proximate to or containing vascular endothelial cells, which express an extracellular domain of PSMA. The labeled biological agents can also be used to detect normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof. They also can be used alone or bound to a substance effective to ablate or kill such cells as a therapy for prostate or other cancers. Also disclosed are four hybridoma cells lines, each of which produces a monoclonal antibody recognizing extracellular domains of PSMA of normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof.

Abstract: Methods of treating cancer in a patient are provided. In some embodiments the method comprises administering an antibody that is capable of binding to the extracellular domain of PSMA after first administering a hormonal therapy.

Abstract: Use of antibodies or binding portions thereof, probes, ligands, or other biological agents which either recognize an extracellular domain of prostate specific membrane antigen (PSMA) or bind to and are internalized with PSMA. These biological agents can be labeled and used for detection of cancerous tissues, particularly cancerous tissues proximate to or containing vascular endothelial cells, which express an extracellular domain of PSMA. The labeled biological agents can also be used to detect normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof. They also can be used alone or bound to a substance effective to ablate or kill such cells as a therapy for prostate or other cancers. Also disclosed are four hybridoma cells lines, each of which produces a monoclonal antibody recognizing extracellular domains of PSMA of normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof.

Abstract: Anti-androgen therapies represent the cornerstone of prostate cancer (PC) treatment. Yet all PC patients ultimately fail efforts to rein in the androgen receptor (AR). This invention is based on the discovery that prostate-specific membrane antigen (PSMA), a highly PC-specific and clinically validated cell surface target, is AR-suppressed and up-regulated in PC as a result of hormonal manipulation. This up-regulation occurs in an unexpected timeframe and it occurs even in the castrate-resistant setting. As a result, hormonal therapy creates a state of conditionally enhanced vulnerability of PC to PSMA-targeted anti-cancer/cytotoxic agents that can be exploited by leveraging anti-AR therapy by the addition of PSMA-targeted agents. We demonstrate this conditionally enhanced vulnerability in a castrate-resistant animal model. The state of conditionally enhanced vulnerability may be relevant for other cancer targets and efforts to screen for them may improve other cancer therapies.

Abstract: Methods of treating cancer in a patient are provided. In some embodiments the method comprises administering an antibody that is capable of binding to the extracellular domain of PSMA. In some embodiments, the method comprises restricting folate intake by the patient. Methods of monitoring cancer therapy are provided as well as kits for treating cancer and kits for monitoring cancer therapy.

Abstract: The present invention is directed to the use of antibodies or binding portions thereof, probes, ligands, or other biological agents which either recognize an extracellular domain of prostate specific membrane antigen or bind to and are internalized with prostate specific membrane antigen. These biological agents can be labeled and used for detection of normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof. They also can be used alone or bound to a substance effective to ablate or kill such cells as a therapy for prostate cancer. Also disclosed are four hybridoma cell lines, each of which produces a monoclonal antibody recognizing extracellular domains of prostate specific membrane antigens of normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof.

Abstract: Modified antibodies, or antigen-binding fragments thereof, to the extracellular domain of human prostate specific membrane antigen (PSMA) are provided. The modified anti-PSMA antibodies, or antigen-binding fragments thereof, have been rendered less immunogenic compared to their unmodified counterparts to a given species, e.g., a human. Pharmaceutical compositions including the aforesaid antibodies, nucleic acids, recombinant expression vectors and host cells for making such antibodies and fragments are also disclosed. Methods of using the antibodies of the invention to detect human PSMA, or to ablate or kill a PSMA-expressing cell, e.g., a PSMA-expressing cancer or prostatic cell, either in vitro or in vivo, are also provided.