Methods and Compositions for Treating Prostate Cancer Using DNA Vaccines

Abstract

A DNA vaccine for the treatment of prostate cancer, comprising a plasmid vector comprising a nucleotide sequence encoding prostatic acid phosphatase (PAP) operably linked to a transcription regulatory element, wherein upon administration to a mammal a cytotoxic immune reaction against cells expressing PAP is induced. In preferred embodiment, the PAP encoded is a xenoantigen highly homologous to the autoantigen PAP of the mammal. Also disclosed are methods for inducing prostatitis, or inducing immune reaction to PAP, or treating prostate cancer in a mammal, using the DNA vaccine and pharmaceutical compositions comprising the vaccine. Preferably, xenoantigen vaccination is followed by boosting with autoantigen PAP from the same animal species as the mammal being treated.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation application of U.S. application Ser. No. 10 / 669,474 filed on Sep. 25, 2003, which claims the benefit of U.S. provisional application Ser. No. 60 / 413,777, filed Sep. 27, 2002.FIELD OF THE INVENTION [0002] This invention relates to pharmaceutical compositions and methods using plasmid DNA vaccines for the treatment of prostate cancer. Specifically, this invention relates to the use of plasmids comprising a gene or polynucleotide sequence encoding prostatic acid phosphatase (PAP) for cancer the treatment of prostate. BACKGROUND OF THE INVENTION [0003] Prostate cancer continues to be a major health problem worldwide, with over 220,000 estimated new cases this year in the United States alone (Jemal et al., Cancer Statistics, 2003. (2003) CA A Canc. Jour. Clin., 53:5-26). It is the most common tumor diagnosed among men and the second leading cause of male cancer-related death in the United States (Jemal et a...

AI Technical Summary

Benefits of technology

The invention provides a method for inducing an immune reaction to prostatic acid phosphatase (PAP) in a mammal in need thereof. This is achieved by administering a recombinant DNA construct containing a polynucleotide sequence encoding PAP operatively linked to a transcriptional regulatory element. The method can induce both humoral and cellular immune reactions against PAP, leading to destructive prostatitis and selective killing of cancer cells expressing PAP. The method can also be employed using a "prime-boost" strategy, where two different polynucleotide sequences are used to induce the immune reaction. A DNA vaccine is also contemplated, which comprises a plasmid vector containing a polynucleotide sequence encoding PAP operatively linked to a transcription regulatory element. The pharmaceutical composition of the invention includes the DNA vaccine and a suitable amount of immunostimulant.

Problems solved by technology

At present, there is no accepted adjuvant treatment for patients undergoing radical prostatectomy or ablative radiation therapy that has been shown to prevent the progression to metastatic disease.

These findings suggest that patients with stage D0 disease are at high risk for progressive disease, however with a long window of time to test adjuvant therapies.

At present, the best treatment for these patients is controversial, with some obtaining radical prostatectomy, other referred for radiation therapy with or without androgen deprivation therapy, and yet others are expectantly observed without specific treatment.

Moreover, prostate cancer is a slow-growing disease, with typically over five years from the time of diagnosis of organ-confined disease to the development of clinically apparent metastatic disease.

Dendritic cell-based vaccines, however, must be individualized for each patient, and as a consequence are costly and cumbersome in large-scale application.

Protein based vaccines, on the other hand, are taken up by antigen presenting cells and expressed predominantly in the context of MHC class II, thus often are difficult to be delivered effectively and may not induce robust immune response to the antigen.

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