Initial results of a phase II trial of patients with extensive stage small cell lung cancer (SCLC) immunized with dendritic cells (DC) transduced with wild-type p53

Abstract

2543 Background: Many types of cancer are associated with mutations in the p53 gene. Patients with SCLC exhibit a very high frequency of p53 mutations, which result in overexpression of p53 protein in tumor cells. In preclinical studies we and others have demonstrated that tumor cells can be recognized by p53-specific cytotoxic T cells. Here, we tested this concept in clinical trial. Methods: Twenty-two patients with extensive stage SCLC were treated to date in an on-going phase II trial. Patients received first-line chemotherapy to best response, and those patients with stable disease or minor progression underwent leukapheresis 8 weeks after the last dose of chemotherapy. DC were generated from peripheral blood precursors and then infected with adenoviral construct containing wild-type p53 (ADVEXIN). Patients received 3 doses of vaccine i.d. (2–5x106 p53+ DCs per dose). p53 specific immune response was evaluated using ELISPOT and staining with tetramers. Results: The vaccine was well tolerated, and no a...