Immunotherapy of epithelial tumors using intralesional injection of antigens that induce a delayed type hypersensitivity reaction

Abstract

The pharmaceutical composition is useful for treating epithelial tumors in a subject and contains at least two antigens and a pharmaceutically acceptable carrier, where each of the antigens induces or is capable of inducing a cutaneous delayed type hypersensitivity (DTH) response in the subject. This composition is particularly useful in treating epithelial tumors, such as warts or verrucae, that are induced by or related to papillomavirus. Antigens useful in the present pharmaceutical composition are anergy panel antigens, such as killed mumps virus, candida extract, trichophyton extract or comparable antigenic extracts. An additional pharmaceutical composition, also useful for treating epithelial tumors, contains at least one antigen that induces or is capable of inducing a cutaneous DTH response in a subject, at least one cytokine or colony stimulating factor and a pharmaceutically acceptable carrier. Kits containing these pharmaceutical compositions are useful for this immunotherapy.

We claim:  
     
         1 . A pharmaceutical composition for treating an epithelial tumor in a subject comprising at least two antigens and a pharmaceutically acceptable carrier, wherein each of said antigens induces or is capable of inducing a cutaneous delayed type hypersensitivity response in the subject.  
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein said epithelial tumor is caused by a virus.  
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein said virus is a papilloma virus.  
     
     
         4 . The pharmaceutical composition of  claim 3 , where said virus is a human papilloma virus.  
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein said epithelial tumor is a verruca, a condyloma, a cervical carcinoma, bowenoid papulosis, a laryngeal papilloma, epidermodysplasia verruciformis or a melanoma.  
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein said verruca is verruca vulgaris, verruca plantaris, verruca palmeris or verruca plana.  
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein said antigens are antigenic determinants, haptens or epitopes of said antigens and are responsible for inducing said delayed type hypersensitivity response in the subject.  
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein said antigens are selected from the group consisting of viral, fungal, bacterial and a combination thereof.  
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein said antigens are selected from the group consisting of candida, trichophyton, mumps and a combination thereof.  
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein said antigens are a combination of candida, trichophyton and mumps.  
     
     
         11 . The pharmaceutical composition of  claim 1 , further comprising at least one cytokine or colony stimulating factor into said tumor.  
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein said colony stimulating factor is granulocyte macrophage colony stimulating factor and said cytokine is interferon-α, interferon-β, interferon-γ, interleukin-2 or interleukin-12.  
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein said subject is a mammal.  
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein said mammal is a human, rabbit, canine, feline, bovine, equine, or ovine.  
     
     
         15 . A kit comprising at least one container, a hypodermic needle or a high pressure injection device comprising the pharmaceutical composition of  claim 1 .  
     
     
         16 . A kit of  claim 15 , further comprising at least one container, a hypodermic needle or a high pressure injection device comprising at least one additional pharmaceutical composition comprising at least one cytokine or colony stimulating factor into said tumor.  
     
     
         17 . A kit comprising at least one container, a hypodermic needle or a high pressure injection device comprising the pharmaceutical composition of  claim 11 .  
     
     
         18 . A pharmaceutical composition for treating an epithelial tumor in a subject comprising at least one antigen, at least one cytokine or colony stimulating factor and a pharmaceutically acceptable carrier, wherein said antigen induces or is capable of inducing a cutaneous delayed type hypersensitivity response in the subject.  
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein said epithelial tumor is caused by a virus.  
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein said virus is a papilloma virus.  
     
     
         21 . The pharmaceutical composition of  claim 20 , where said virus is a human papilloma virus.  
     
     
         22 . The pharmaceutical composition of  claim 18 , wherein said epithelial tumor is a verruca, a condyloma, a cervical carcinoma, bowenoid papulosis, a laryngeal papilloma, epidermodysplasia verruciformis or a melanoma.  
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein said verruca is verruca vulgaris, verruca plantaris, verruca palmeris or verruca plana.  
     
     
         24 . The pharmaceutical composition of  claim 18 , wherein said antigen is an antigenic determinant, a hapten or an epitope of said antigen and is responsible for inducing said delayed type hypersensitivity response in the subject prior.  
     
     
         25 . The pharmaceutical composition of  claim 18 , wherein said antigen is selected from the group consisting of viral, fungal, bacterial and a combination thereof.  
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein said antigen is selected from the group consisting of candida, trichophyton, mumps and a combination thereof.  
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein said antigen is a combination of candida, trichophyton and mumps.  
     
     
         28 . The pharmaceutical composition of  claim 18 , wherein said colony stimulating factor is granulocyte macrophage colony stimulating factor and said cytokine is interferon-α, interferon-β, interferon-γ, interleukin −2 or interleukin-12.  
     
     
         29 . The pharmaceutical composition of  claim 18 , wherein said subject is a mammal.  
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein said mammal is a human, rabbit, canine, feline, bovine, equine, or ovine.  
     
     
         31 . A kit comprising at least one container comprising the pharmaceutical composition of  claim 18 .  
     
     
         32 . A kit of claim  31  further comprising at least one container, a hypodermic meedle or a high pressure injection device comprising at least one additional antigen that induces or is capable of inducing a cutaneous delayed type hypersensitivity response in the subject, at least one cytokine or colony stimulating factor or a combination thereof.