Methods for improving medical therapies

Abstract

Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.

We claim the following: 
     
         1 . A method for enhancing the effectiveness of a medical therapy in a subject comprising administering to the subject an agent that suppresses a biological damage response inducible by the medical therapy, wherein the agent is administered prior to, subsequent to, or concurrent with administration of the medical therapy. 
     
     
         2 . The method of  claim 1  wherein the agent is administered to the subject at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 10 days, at least 30, at least 60, or at least 90 days subsequent to administration of the medical therapy. 
     
     
         3 . The method of either  claim 1  or  claim 2  wherein the agent that suppresses the biological damage response selectively destroys or facilitates selective destruction of one or more senescent cells. 
     
     
         4 . The method of  claim 1  wherein the agent is administered to the subject prior to administration of the medical therapy. 
     
     
         5 . The method of  claim 4  wherein the agent is administered to the subject at least 1 day, at least 2-6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4-5 weeks, at least 6-8 weeks, or at least 10-12 weeks prior to administration of the medical therapy. 
     
     
         6 . The method of  claim 1  wherein the agent is administered concurrently with at least a portion of the administered medical therapy. 
     
     
         7 . The method of any one of  claims 1 - 6  wherein the agent that suppresses the biological damage response inhibits expression or secretion of one or more senescence cell-associated molecules produced by a senescent cell. 
     
     
         8 . The method of any one of  claims 1 - 7  wherein the agent is a small molecule, polypeptide, peptide, antibody, antigen-binding fragment, peptibody, recombinant viral vector, or a nucleic acid. 
     
     
         9 . The method of any one of  claims 1 - 8  wherein the medical therapy increases the proportion of senescent cells in a subject. 
     
     
         10 . The method of any one of  claims 1 - 9  wherein the medical therapy comprises radiation, a chemotherapy, an anti-viral therapy, or a hormone. 
     
     
         11 . The method of any one of  claims 1 - 10  wherein the subject has a cancer, is in cancer remission, is at risk of developing a recurrence of a cancer, or is at risk of developing a cancer, and wherein the medical therapy comprises an anti-cancer therapy. 
     
     
         12 . The method of  claim 11 , wherein the cancer comprises a solid tumor or a liquid tumor. 
     
     
         13 . The method of either  claim 11  or  claim 12 , wherein the cancer is metastatic cancer. 
     
     
         14 . The method of  claim 10  wherein the anti-viral therapy is an HIV/AIDS management therapy. 
     
     
         15 . The method of  claim 14  wherein the HIV/AIDS management therapy comprises a highly active antiretroviral therapy (HAART). 
     
     
         16 . The method of any one of  claims 1 - 13  wherein the subject has a cancer and has received or will receive a stem cell transplant, and wherein the medical therapy is high dose chemotherapy or high dose radiotherapy or a combination thereof. 
     
     
         17 . The method of  claim 16  wherein the stem cell transplant is selected from (a) an autologous stem cell transplant, and (b) an allogenic stem cell transplant. 
     
     
         18 . The method of any one of  claims 1 - 10  wherein the subject has a cardiovascular disease or is at risk of developing a cardiovascular disease, and wherein the medical therapy is angiotensin. 
     
     
         19 . The method of any one of  claims 1 - 10  wherein the subject has diabetes, and wherein the medical therapy is insulin. 
     
     
         20 . A method for enhancing the effectiveness of a medical therapy in a subject comprising:
 (a) administering to the subject the medical therapy, which medical therapy induces senescence in one or more cells of the subject; and then   (b) administering to the subject an anti-senescent cell agent, which agent selectively destroys or facilitates the selective destruction of the one or more senescent cells.   
     
     
         21 . The method of  claim 20 , wherein the agent is administered to the subject at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, or at least 10 days, at least 30 days, at least 60 days, or at least 90 days subsequent to administration of the medical therapy. 
     
     
         22 . The method of either  claim 20  or  21 , wherein the agent is a small molecule, polypeptide, peptide, antibody, antigen-binding fragment, peptibody, recombinant viral vector, or a nucleic acid. 
     
     
         23 . The method of any one of  claims 20 - 22  wherein the medical therapy increases the proportion of senescent cells in a subject. 
     
     
         24 . The method of any one of  claims 20 - 23  wherein the medical therapy comprises radiation, a chemotherapy, an anti-viral therapy, or a hormone. 
     
     
         25 . The method of any one of  claims 20 - 24  wherein the subject has a cancer, is in cancer remission, is at risk of developing a recurrence of a cancer, or is at risk of developing a cancer, and wherein the medical therapy comprises an anti-cancer therapy. 
     
     
         26 . The method of  claim 25 , wherein the cancer comprises a solid tumor or a liquid tumor. 
     
     
         27 . The method of either  claim 25  or  claim 26 , wherein the cancer is metastatic cancer. 
     
     
         28 . The method of  claim 24  wherein the anti-viral therapy is an HIV/AIDS management therapy. 
     
     
         29 . The method of  claim 28  wherein the HIV/AIDS management therapy comprises a highly active antiretroviral therapy (HAART). 
     
     
         30 . The method of any one of  claims 20 - 27 , wherein the subject has a cancer and has received or will receive a stem cell transplant, and wherein the medical therapy comprises high dose chemotherapy or high dose radiotherapy or a combination thereof. 
     
     
         31 . The method of  claim 30  wherein the stem cell transplant is selected from (a) an autologous stem cell transplant, and (b) an allogenic stem cell transplant. 
     
     
         32 . The method of any one of  claims 20 - 24  wherein the subject has a cardiovascular disease or is at risk of developing a cardiovascular disease, and wherein the medical therapy is angiotensin. 
     
     
         33 . The method of any one of  claims 20 - 24  wherein the subject has diabetes, and wherein the medical therapy is insulin. 
     
     
         34 . Use of an agent that suppresses a biological damage response inducible by a medical therapy for enhancing the effectiveness of the medical therapy, wherein the agent is suitable for administration prior to, subsequent to, or concurrent with administration of the medical therapy. 
     
     
         35 . The use of  claim 34  wherein the agent is suitable for administration at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 10 days, at least 30, at least 60, or at least 90 days subsequent to administration of the medical therapy. 
     
     
         36 . The use of either  claim 34  or  claim 35  wherein the agent that suppresses the biological damage response selectively destroys or facilitates selective destruction of one or more senescent cells. 
     
     
         37 . The use of  claim 34  wherein the agent is administered prior to administration of the medical therapy. 
     
     
         38 . The use of  claim 37  wherein the agent is administered at least 1 day, at least 2-6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4-5 weeks, at least 6-8 weeks, or at least 10-12 weeks prior to administration of the medical therapy. 
     
     
         39 . The use of  claim 34  wherein the agent is administered concurrently with at least a portion of the administered medical therapy. 
     
     
         40 . The use of  claim 34  wherein the agent that suppresses the biological damage response inhibits expression or secretion of one or more senescence cell-associated molecules produced by a senescent cell. 
     
     
         41 . The use of any one of  claim 34  wherein the agent is a small molecule, polypeptide, peptide, antibody, antigen-binding fragment, peptibody, recombinant viral vector, or a nucleic acid. 
     
     
         42 . The use of  claim 34  wherein the medical therapy increases the proportion of senescent cells in a subject. 
     
     
         43 . The use of  claim 34  wherein the medical therapy comprises radiation, a chemotherapy, an anti-viral therapy, or a hormone. 
     
     
         44 . The use of  claim 34  wherein the medical therapy is an anti-cancer therapy. 
     
     
         45 . The use of  claim 44 , wherein the cancer comprises a solid tumor or a liquid tumor. 
     
     
         46 . The use of either  claim 44  or  claim 45 , wherein the cancer is metastatic cancer. 
     
     
         47 . The use of  claim 43  wherein the anti-viral therapy is an HIV/AIDS management therapy. 
     
     
         48 . The use of  claim 47  wherein the HIV/AIDS management therapy comprises a highly active antiretroviral therapy (HAART). 
     
     
         49 . The use of  claim 34  wherein the medical therapy is high dose chemotherapy or high dose radiotherapy or a combination thereof, which is administered prior to or subsequent to administration of a stem cell transplant. 
     
     
         50 . The use of  claim 49  wherein the stem cell transplant is selected from (a) an autologous stem cell transplant, and (b) an allogenic stem cell transplant. 
     
     
         51 . The use of  claim 34  for treating or preventing a cardiovascular disease wherein the medical therapy is angiotensin. 
     
     
         52 . The use of  claim 1  for treating or preventing diabetes, wherein the medical therapy is insulin. 
     
     
         53 . A use of an anti-senescent cell agent for enhancing the effectiveness of a medical therapy wherein the medical therapy induces senescence in one or more cells, and wherein the agent selectively destroys or facilitates the selective destruction of the one or more senescent cells. 
     
     
         54 . The use of  claim 53 , wherein the agent is suitable for administration at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 7 days, or at least 10 days, at least 30 days, at least 60 days, or at least 90 days subsequent to administration of the medical therapy. 
     
     
         55 . The use of  claim 53 , wherein the agent is a small molecule, polypeptide, peptide, antibody, antigen-binding fragment, peptibody, recombinant viral vector, or a nucleic acid. 
     
     
         56 . The use of  claim 53  wherein the medical therapy increases the proportion of senescent cells. 
     
     
         57 . The use of  claim 53  wherein the medical therapy comprises radiation, a chemotherapy, an anti-viral therapy, or a hormone. 
     
     
         58 . The use of  claim 53  wherein the medical therapy comprises an anti-cancer therapy for treating or preventing a cancer. 
     
     
         59 . The use of  claim 58 , wherein the cancer comprises a solid tumor or a liquid tumor. 
     
     
         60 . The use of  claim 58 , wherein the cancer is metastatic cancer. 
     
     
         61 . The use of  claim 57  wherein the anti-viral therapy is an HIV/AIDS management therapy. 
     
     
         62 . The use of  claim 61  wherein the HIV/AIDS management therapy comprises a highly active antiretroviral therapy (HAART). 
     
     
         63 . The use of  claim 53  for treatment or prevention of a cardiovascular disease, wherein the medical therapy is angiotensin. 
     
     
         64 . The use of  claim 53  for treating or preventing diabetes, wherein the medical therapy is insulin. 
     
     
         65 . A method of identifying a compound that selectively inhibits the senescence associated secretory phenotype (SASP), said method comprising:
 (a) contacting senescent cells with a candidate agent and contacting quiescent cells with the candidate agent;   (b) determining the level of one or more senescence associate molecules produced by the senescent cells and by the quiescent cells;   (c) determining viability of the senescent cells and quiescent cells; and   (d) comparing the level of the one or more senescence associate molecules produced by the senescent cells with the level of the one or more senescence associate molecules produced by the quiescent cells,   wherein reduction in the level of one or more senescence associated molecules produced by the senescent cells compared with reduction in the level of the one or more senescence associated molecules produced by the quiescent cells, and wherein viability of the senescence cells and the quiescent cells is not reduced in the presence of the candidate agent identifies a compound that selectively inhibits the senescence associated secretory phenotype.   
     
     
         66 . The method according of  claim 65 , wherein said one or more components characteristic of the SASP comprises one or more components selected from the group consisting of IL-6, IL-8, GM-CSF, MCP3, IGF1, PDGF-BB, EGF, BMP4, and MCP-2. 
     
     
         67 . The method of  claim 65  or  66 , wherein said method is performed in a high throughput screening (HTS) format.