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

• US 6,350,451 B1
• Filed: 06/25/1999
• Issued: 02/26/2002
• Est. Priority Date: 06/25/1999
• Status: Expired due to Term

• Current Assignee: Bioventures, LLC
• Original Assignee: The Board of Trustees of the University of Arkansas (University of Arkansas System)
• Inventors: Horn, Thomas Dag, Johnson, Sandra Marchese
• Primary Examiner(s): Caputa, Anthony C.
• Assistant Examiner(s): Nickol, Gary B.
• Application Number:
  US09/344,357
• Time in Patent Office: 977 Days
• Field of Search: 424/184.1, 424/193.1, 424/196.11, 424/201.1, 424/212.1, 424/274.1, 424/85.2
• US Class Current: 424/184.1
• CPC Class Codes: A61K 2039/58 raising an immune response against a target which is not the antigen used for immunisation
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 39/0002 Fungal antigens, e.g. Trichophyton, Aspergillus, Candida
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/165 Mumps or measles virus
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present immunotherapy relates to a method of treating epithelial tumors and the pharmaceutical compositions and kits useful in treating such tumors. The immunotherapy comprises injecting an effective amount of a pharmaceutical composition containing at least one antigen into the tumor, wherein the antigen is selected for inducing or having the ability to induce a cutaneous delayed type hypersensitivity (DTH) response in the subject prior to the injection of the antigen into the tumors. This immunotherapy 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 immunotherapy are anergy panel antigens, such as killed mumps virus, candida extract, trichophyton extract or comparable antigenic extracts. Additionally, the method optionally includes the injection of an effective amount of at least one cytokine or colony stimulating factor into the tumor either simultaneously with or sequentially to the injection of the antigen. The subject treated by the present immunotherapy is preferably a mammal selected from a human, canine, bovine, feline, equine, ovine or rabbit subject.

Claims

1. A method of treating at least one benign epithelial tumor in a subject comprising injecting an effective amount sufficient to cause regression of said tumor of a pharmaceutical composition comprising an antigen selected from the group consisting of mumps, candida, trichophyton and a combination thereof, into at least one of said tumor in said subject, wherein said tumor is caused by a papilloma virus, and wherein said antigen induces or is capable of inducing a cutaneous delayed type hypersensitivity response in said subject.

2. The method of claim 1, where said papilloma virus is a human papilloma virus.

3. The method of claim 1, wherein said epithelial tumor is a verruca, a condyloma, bowenoid papulosis, a laryngeal papilloma, or epidermodysplasia verruciformis.

4. The method of claim 3, wherein said verruca is verruca vulgaris, verruca plantaris, verruca palmeris or verruca plana.

5. The method of claim 1, further comprising injecting at least one additional pharmaceutical composition containing at least one cytokine or colony stimulating factor into said tumor.

6. The method of claim 5, wherein said colony stimulating factor is granulocyte macrophage colony stimulating factor.

7. The method of claim 5, wherein said cytokine is interferon-α

, interferon-β

, interferon-γ

, interleukin-2 or interleukin-12.

8. The method of claim 5, wherein said injection of said cytokine or colony stimulating factor is simultaneous with or sequential to the injection of said antigen.

9. The method of claim 1, wherein said injection of said antigen is performed via a hypodermic needle or high pressure injection sufficient for the antigen to enter at least the epidermis or dermis of said subject.

10. The method of claim 5, wherein said injection of said antigen and said cytokine or colony stimulating factor is performed via a hypodermic needle or high pressure injection sufficient for the antigen to enter at least the epidermis or the dermis of said subject.

11. The method of claim 1, wherein said subject is a mammal.

12. The method of claim 11, wherein said mammal is a human, rabbit, canine, feline, bovine, equine, or ovine.

13. The method of claim 1, wherein said pharmaceutical composition comprises a mumps antigen.

14. The method of claim 1, wherein said pharmaceutical composition comprises a candida antigen.

15. The method of claim 1, wherein said pharmaceutical composition comprises a trichophyton antigen.

16. The method of claim 1, wherein said pharmaceutical composition comprises at least two of said antigens or a combination thereof.

17. The method of claim 1, wherein said composition comprises mumps, candida and trichophyton antigens.