Combined tumor suppressor gene therapy and chemotherapy in the treatment of neoplasms

Abstract

In one embodiment, this invention provides methods of treating mammalian cancer or hyperproliferative cells, said method comprising contacting said cells with a tumor suppressor protein or tumor suppressor nucleic acid and also contacting said cell with at least one adjunctive anti-cancer agent. The invention also provides for a pharmacological composition comprising a tumor suppressor protein or a tumor suppressor nucleic acid and at least one adjunctive anti-cancer agent, and a kit for the treatment of mammalian cancer or hyperproliferative cells.

1 . A kit for the treatment of mammalian cancer or hyperproliferative cells, said kit comprising: 
 a first container comprising a tumor suppressor nucleic acid selected from the group consisting of wild-type p53 nucleic acid, or a retinoblastoma (RB) nucleic acid; and    a second container comprising at least one anti-mitotic agent;    wherein the mammalian cancer cells or hyperproliferative cells comprise a member selected from the group consisting of a human head and neck cell, an ovarian cell, a prostate cell, and a breast cell.    
   
   
       2 . The kit of  claim 1 , wherein said tumor suppressor nucleic acid encodes a wild-type p53 protein.  
   
   
       3 . The kit of  claim 1 , wherein said anti-mitotic agent is paclitaxel or a paclitaxel derivative.  
   
   
       4 . The kit of  claim 1 , further comprising instructions describing the administration of both said tumor suppressor nucleic acid and said anti-mitotic agent to inhibit the growth or proliferation of said cells.  
   
   
       5 . The kit of  claim 1 , wherein said tumor suppressor nucleic acid is selected from the group consisting of p53, p110 RB , and p56 RB .  
   
   
       6 . The kit of  claim 1 , wherein said first container contains a nucleic acid that is contained in a recombinant adenoviral vector.  
   
   
       7 . The kit of  claim 6 , wherein said nucleic acid is contained in a recombinant adenoviral vector comprising a partial or total deletion of a protein IX DNA and comprising a nucleic acid encoding a p53 protein.  
   
   
       8 . The kit of  claim 7 , wherein said deletion of the protein IX gene sequence extends from about 3500 bp from the 5′ viral terminus to about 4000 bp from the 5′ viral terminus.  
   
   
       9 . The kit of  claim 8 , wherein the adenoviral vector further comprises a deletion of DNA sequence designated E1a and E1b.  
   
   
       10 . The kit of  claim 6 , wherein said recombinant adenoviral vector comprises the adenovirus type 2 major late promoter or the human CMV promoter, the adenovirus type 2 tripartite leader cDNA and a human p53 cDNA.  
   
   
       11 . The kit of  claim 6 , wherein said vector is A/C/N/53.  
   
   
       12 . A pharmacological composition for treating mammalian cancer cells or hyperproliferative cells, comprising a tumor suppressor nucleic acid and at least one anti-mitotic agent, wherein the mammalian cancer cells or hyperproliferative cells comprise a member selected from the group consisting of a human head and neck cell, an ovarian cell, a prostate cell, and a breast cell.  
   
   
       13 . The composition of  claim 12 , wherein said anti-mitotic agent is paclitaxel or a paclitaxel derivative.  
   
   
       14 . The composition of  claim 12 , wherein said tumor suppressor nucleic acid is selected from the group consisting of a nucleic acid that encodes a wild-type p53 protein, and a nucleic acid that encodes a retinoblastoma (RB) protein.  
   
   
       15 . The composition of  claim 12 , wherein said nucleic acid encodes a wild-type p53 protein.  
   
   
       16 . The composition of  claim 12 , wherein said nucleic acid encodes a said retinoblastoma p110 RB  or a p56 RB .  
   
   
       17 . The composition of  claim 12 , wherein said nucleic acid is contained in recombinant adenoviral vector.  
   
   
       18 . The composition of  claim 17 , wherein said nucleic acid is contained in a recombinant adenoviral vector comprising a partial or total deletion of a protein IX DNA and comprising a nucleic acid encoding a P53 protein.  
   
   
       19 . The composition of  claim 18 , wherein said deletion of the protein IX gene sequence extends from about 3500 bp from the 5′ viral terminus to about 4000 bp from the 5′ viral terminus.  
   
   
       20 . The composition of  claim 19 , wherein the adenoviral vector further comprises a deletion of DNA sequence designated E1a and E1b.  
   
   
       21 . The composition of  claim 17 , wherein said recombinant adenoviral vector comprises the adenovirus type 2 major late promoter or the human CMV promoter, the adenovirus type 2 tripartite leader cDNA and a human p53 cDNA.  
   
   
       22 . The composition of  claim 17 , wherein said vector is A/C/N/53.  
   
   
       23 . The composition of  claim 13 , wherein said paclitaxel or paclitaxel derivative is paclitaxel.  
   
   
       24 . A composition comprising 
 a mammalian cancer or hyperproliferative cell, wherein said cell contains an exogenous tumor suppressor nucleic acid; and    paclitaxel or a paclitaxel derivative.    
   
   
       25 . The composition of  claim 24 , wherein said tumor suppressor nucleic acid is a nucleic acid that encodes a tumor suppressor protein selected from the group consisting of wild-type p53 protein, and a retinoblastoma (RB) protein.  
   
   
       26 . The composition of  claim 24 , wherein said tumor suppressor nucleic acid encodes a wild-type p53 protein.  
   
   
       27 . The composition of  claim 25 , wherein said retinoblastoma protein is a p110 RB  or a p56 RB .  
   
   
       28 . The composition of  claim 24 , wherein said cell is present in a mammal.  
   
   
       29 . The composition of  claim 24 , wherein said cell comprises a neoplastic cell.  
   
   
       30 . The composition of  claim 29 , wherein said neoplastic cell comprises a cancer cell selected from the group consisting of an ovarian cancer cell, a pancreatic cancer cell, a non-small cell lung cancer cell, a small cell lung cancer cell, a hepatocarcinoma cell, a melanoma cell, a retinoblastoma cell, a breast tumor cell, a colorectal carcinoma cell, a leukemia cell, a lymphoma cell, a brain tumor cell, a cervical carcinoma cell, a sarcoma cell, a prostate tumor cell, a bladder tumor cell, a tumor cell of the reticuloendothelial tissues, a Wilm's tumor cell, an astrocytoma cell, a glioblastoma cell, a neuroblastoma cell, an osteosarcoma cell, a renal cancer cell, and a head and neck cancer cell.  
   
   
       31 . The composition of  claim 24 , wherein the mammalian cancer cell or hyperproliferative cell comprises a member selected from the group consisting of a human head and neck cell, an ovarian cell, a prostate cell, and a breast cell.  
   
   
       32 . The composition of  claim 24 , wherein the mammalian cancer or hyperproliferative cell is deficient in endogenous p53 tumor suppressor nucleic acid.