Assuntos
Células Epiteliais/efeitos dos fármacos , Fármacos Gastrointestinais/uso terapêutico , Imunidade nas Mucosas/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/uso terapêutico , Animais , Moléculas de Adesão Celular/metabolismo , Células Epiteliais/enzimologia , Células Epiteliais/imunologia , Humanos , Doenças Inflamatórias Intestinais/enzimologia , Doenças Inflamatórias Intestinais/imunologia , Mucosa Intestinal/enzimologia , Mucosa Intestinal/imunologia , Terapia de Alvo Molecular , Fosforilação , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/metabolismo , Transdução de Sinais/efeitos dos fármacos , TirosinaRESUMO
OBJECTIVE: The field of cancer vaccine therapy is currently expected to become the fourth option in the treatment of cancer after surgery, chemotherapy and radiation therapy. We developed a novel cancer peptide vaccine therapy for bladder cancer through a genome-wide expression profile analysis. METHODS: Among a number of oncoproteins that are transactivated in cancer cells, we focused on M phase phosphoprotein 1 and DEP domain containing 1, both of which are cancer-testis antigens playing critical roles in the growth of bladder cancer cells, as candidate molecules for the development of drugs for bladder cancer. In an attempt to identify the peptide epitope from these oncoantigens, we conducted a clinical trial using these peptides for patients with advanced bladder cancer. RESULTS: We identified HLA-A24-restricted peptide epitopes corresponding to parts of M phase phosphoprotein 1 and DEP domain containing 1 proteins, which could induce peptide-specific cytotoxic T lymphocytes. Using these peptides, we found that M phase phosphoprotein 1- and DEP domain containing 1-derived peptide vaccines could be well tolerated without any serious adverse events, and effectively induced peptide-specific cytotoxic T lymphocytes in vivo. CONCLUSIONS: The novel approach adopted in the treatment with peptide vaccines is considered to be a promising therapy for bladder cancer.