CT-011 and p53 Genetic Vaccine for Advanced Solid Tumors

Background: * PD1 is an inhibitory receptor that belongs to CD28-B7 family. * PD1 binds to two ligands PD-L1 and PD-L2 to down modulate T-cell immune responses. * PD1 is expressed on T cells, B cells, and NK cells. * The over expression of PD-1 ligand (PD-L1) in tumors is associated with an immune suppression and poor prognosis. Objectives: * To determine the safety and tolerability of escalating doses of anti PD1 antibody (CT-011) in combination with subcutaneous p53 vaccine. * To determine the immune response to wt p53 (264-272) peptide. * To determine the clinical efficacy of this combination. Eligibility: * 18 years of age or older, not pregnant or nursing and not immunocompromised or having an autoimmune disease. * HLA-A2 haplotype. * ECOG performance status of 0-1. * Advanced solid tumors over expressing p53 protein with a histological confirmation of the original primary tumor via the Pathology Laboratory, CCR , NCI. Design: * Single arm, pilot/phase I trial in patients receiving a fixed dose of vaccine in combination with an escalating dose of CT-011. * The vaccine will be administered subcutaneously every 3 weeks followed by CT-011 two days after each vaccine until disease progression or toxicity. * Patients will undergo blood draw or aphaeresis for immunologic assays prior to starting treatment and after every second cycle. * Patients will be assessed for overall safety, immunologic efficacy, tumor response using RECIST criteria and survival. * Patients will be followed for up to two years after the last vaccination for assessment of safety and efficacy.