P53 vaccines for the treatment of cancers

Abstract

The present invention relates to immunotherapy methods for treating hyperproliferative disease in humans, particularly to hyperproliferative disease that is refractory to therapy. More specifically, the invention is directed, in one embodiment, to methods for treating a subject with a hyperproliferative disease in which the expression of a self gene is upregulated in therapy-resistant hyperproliferative cells. In another embodiment, an adenoviral expression construct comprising a self gene under the control of a promoter operable in eukaryotic cells is administered to the therapy-resistant hyperproliferative cells. The present invention thus provides immunotherapies for treating therapy-resistant hyperproliferative disease by attenuating the natural immune system's CTL response against hyperproliferative cells or overexpressing mutant p53 antigens, for example.

1 . A method of conferring or restoring sensitivity to one or more therapy-resistant hyperproliferative cells in a subject, wherein said hyperproliferative cells are characterized by alteration or increased expression of a self gene product, comprising providing to said subject a dendritic cell expressing said self gene product. 
     
     
         2 . The method of  claim 1 , wherein the therapy-resistant hyperproliferative cells are further defined as resistant to a drug, radiation, or both. 
     
     
         3 .- 22 . (canceled) 
     
     
         23 . The method of  claim 1 , further comprising administering to said subject an additional therapy. 
     
     
         24 . The method of  claim 23 , wherein the additional therapy comprises a drug, a metal, radiation, surgery, gene therapy, immunotherapy, hormone therapy, or a combination thereof. 
     
     
         25 . The method of  claim 23 , wherein the additional therapy comprises chemotherapy. 
     
     
         26 . The method of  claim 25 , wherein the chemotherapy comprises a composition that upregulates expression of p53, Fas, a death receptor, or a combination thereof. 
     
     
         27 . The method of  claim 23 , wherein the dendritic cell and the additional therapy are provided to the subject concomitantly or in succession. 
     
     
         28 . The method of  claim 27 , wherein the dendritic cell is provided to the subject prior to the further therapy. 
     
     
         29 . The method of  claim 28 , wherein the additional therapy is provided to the subject within about one to twelve months of providing the dendritic cell to the subject. 
     
     
         30 . The method of  claim 23 , wherein the dendritic cell and the additional therapy are provided more than once. 
     
     
         31 .- 33 . (canceled) 
     
     
         34 . The method of  claim 1 , wherein providing comprises administering a dendritic cell transformed with an expression construct expressing said self gene product. 
     
     
         35 . The method of  claim 1 , wherein providing comprises administering an expression construct expressing said self gene product to a dendritic cell in said subject. 
     
     
         36 . The method of  claim 35 , wherein the expression construct comprises an adenoviral vector. 
     
     
         37 . The method of  claim 35 , wherein said self gene product comprises p53. 
     
     
         38 .- 58 . (canceled) 
     
     
         59 . A method of treating one or more hyperproliferative cells in a subject, wherein said one or more hyperproliferative cells are resistant to a clinically-recognized therapy for the hyperproliferative cells or wherein said one or more hyperproliferative cells will become resistant upon exposure to the clinically-recognized therapy for the hyperproliferative cells, and wherein the hyperproliferative cells are characterized by alteration or increased expression of a self gene product, comprising providing to said subject a dendritic cell expressing said self gene product. 
     
     
         60 .- 61 . (canceled) 
     
     
         62 . A method of treating or preventing the development of therapy-resistant hyperproliferative cells, wherein said hyperproliferative cells are characterized by alteration or increased expression of a self gene product, comprising providing to said subject a dendritic cell expressing said self gene product.