Combination therapy with cd4 lymphocyte depletion and mtor inhibitors

Abstract

The invention provides methods for treating a malignant neoplastic cell proliferative disorder or disease, comprising administering to a subject in need thereof an effective amount of an mTOR inhibitor and an effective amount of a CD4 lymphocyte depleting agent. Such methods find utility in the treatment of certain subsets of malignant neoplastic cell proliferative disorders or diseases, e.g. renal cell carcinoma and melanoma. The invention also provides for pharmaceutical compositions comprising a therapeutically effective amount of an mTOR inhibitor and an effective amount of a CD4 lymphocyte depleting agent in a pharmaceutically acceptable carrier.

1 - 20 . (canceled) 
     
     
         21 . A method of treating or inhibiting metastasis of a carcinoma or melanoma in a subject in need thereof, wherein the subject has been diagnosed with the carcinoma or melanoma, comprising:
 administering a therapeutically effective amount of an mTOR inhibitor to the subject; and   administering to the subject a therapeutically effective amount of a CD4 lymphocyte depleting agent selected from the group consisting of a small molecule, a peptide, a nucleic acid molecule and a macrolide compound, so as to treat or inhibit metastasis of the carcinoma or melanoma.   
     
     
         22 . The method of  claim 21 , wherein the mTOR inhibitor is selected from the group consisting of (i) temsirolimus (CCI-779) or a pharmaceutical equivalent, analog, derivative or a salt thereof, (ii) Everolimus (RAD001) or a pharmaceutical equivalent, analog, derivative or a salt thereof, and (iii) Rapamycin or a pharmaceutical equivalent, analog, derivative or a salt thereof. 
     
     
         23 . The method of  claim 21 , wherein the mTOR inhibitor and the CD4 lymphocyte depleting agent are administered concurrently. 
     
     
         24 . The method of  claim 21 , wherein the mTOR inhibitor and the CD4 lymphocyte depleting agent are administered sequentially. 
     
     
         25 . The method of  claim 21 , wherein the carcinoma is a renal cell carcinoma. 
     
     
         26 . The method of  claim 21 , wherein the mTOR inhibitor and/or the CD4 lymphocyte depleting agent is administered intravenously, intramuscularly, intraperitoneally, orally or via inhalation. 
     
     
         27 . A method of slowing down a carcinoma or melanoma, lessening the severity of a carcinoma or melanoma or alleviating the severity of a carcinoma or melanoma in a subject, comprising:
 administering a therapeutically effective amount of an mTOR inhibitor to the subject; and   administering to the subject a therapeutically effective amount of a CD4 lymphocyte depleting agent selected from the group consisting of a small molecule, a peptide, a nucleic acid molecule and a macrolide compound, so as to lessen or alleviate the severity of the carcinoma or melanoma.   
     
     
         28 . The method of  claim 27 , wherein the mTOR inhibitor is selected from the group consisting of (i) temsirolimus (CCI-779) or a pharmaceutical equivalent, analog, derivative or a salt thereof, (ii) Everolimus (RAD001) or a pharmaceutical equivalent, analog, derivative or a salt thereof, and (iii) Rapamycin or a pharmaceutical equivalent, analog, derivative or a salt thereof. 
     
     
         29 . The method of  claim 27 , wherein the mTOR inhibitor and the CD4 lymphocyte depleting agent are administered concurrently. 
     
     
         30 . The method of  claim 27 , wherein the mTOR inhibitor and the CD4 lymphocyte depleting agent are administered sequentially. 
     
     
         31 . The method of  claim 27 , wherein the carcinoma is a renal cell carcinoma. 
     
     
         32 . The method of  claim 27 , wherein the mTOR inhibitor and/or the CD4 lymphocyte depleting agent is administered intravenously, intramuscularly, intraperitoneally, orally or via inhalation. 
     
     
         33 . A method of reducing the tumor size of a carcinoma or melanoma in a subject, comprising:
 administering a therapeutically effective amount of an mTOR inhibitor to the subject; and   administering to the subject a therapeutically effective amount of a CD4 lymphocyte depleting agent selected from the group consisting of a small molecule, a peptide, a nucleic acid molecule and a macrolide compound, so as to reduce the tumor size of the carcinoma or melanoma.   
     
     
         34 . The method of  claim 33 , wherein the mTOR inhibitor is selected from the group consisting of (i) temsirolimus (CCI-779) or a pharmaceutical equivalent, analog, derivative or a salt thereof, (ii) Everolimus (RAD001) or a pharmaceutical equivalent, analog, derivative or a salt thereof, and (iii) Rapamycin or a pharmaceutical equivalent, analog, derivative or a salt thereof. 
     
     
         35 . The method of  claim 33 , wherein the mTOR inhibitor and the CD4 lymphocyte depleting agent are administered concurrently. 
     
     
         36 . The method of  claim 33 , wherein the mTOR inhibitor and the CD4 lymphocyte depleting agent are administered sequentially. 
     
     
         37 . The method of  claim 33 , wherein the carcinoma is a renal cell carcinoma. 
     
     
         38 . The method of  claim 33 , wherein the mTOR inhibitor and/or the CD4 lymphocyte depleting agent is administered intravenously, intramuscularly, intraperitoneally, orally or via inhalation.