关键词：肽;胸腔压力;转录(遗传学);疫苗;凋亡;细胞(生物学)
摘 要：The Wilms' tumor gene, WT1, encodes transcription factors that regulate cell proliferation, differentiation, and apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a vaccine comprised of four WT1 heteroclitic peptides that are given together with Montanide and GM-CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and shown to be safe and immunogenic. We have chosen to test the efficacy of this vaccine in MPM patients who have minimal disease burden after completion of multimodality therapy, but remain at exceedingly high risk for recurrence. The specific aim of this project is to conduct a multicenter, blinded, randomized trial comparing treatment with the WT-1 peptide vaccine + Montanide/GM-CSF to treatment with Montanide/GM-CSF alone in patients with MPM who have completed multimodality therapy. The primary endpoint is progression free survival. The trial has opened at Memorial Sloan-Kettering and is actively enrolling patients.