A phase I/II study of a multivalent dendritic cell vaccine in patients with metastatic melanoma

Abstract

2542 Background: Vaccination with dendritic cells (DC), designed to express tumor antigens, is considered to be a possible strategy to elicit anti-tumour immune responses. Effective vaccines that mediate clinical responses in cancer patients may require generation of broad specific cytotoxic T lymphocytes directed against multiple epitopes. Allogeneic lysates from tumor cell lines are an attractive source of antigens as they contain multiple known and unknown tumor associated antigens (TAA). Methods: This is a multicentre, randomised, blinded phase I/II study in patients (pts) with stage IV (AJCC) metastatic melanoma. Safety was the primary objective; immune response (IR) and clinical response, using RECIST criteria, were secondary objectives. Patients were randomised to receive either non matured or matured DC loaded with lysate from 3 melanoma cell lines. DC were obtained from monocytes cultured with IL-13 and GM-CSF and, as required, matured with a bacterial extract and IFN-γ. Six immunizations of ∼2.0 x 107 lysate-loaded DC were administered subcutaneously and intradermally every 4 weeks. Blood samples were collected before each vaccination and IR to lysate or peptides derived from TAA were monitored by proliferation assay and ELISPOT assay for IFN-γ secretion after in vitro stimulation. Results: Sixty melanoma pts were included; 49 received at least one immunisation. No serious adverse events (AE) related to vaccination were observed. The most frequent AE related to treatment was injection site reaction. Increases or inductions in IR to the tumor lysate or TAA-derived peptides were detected after vaccination in one third of evaluable pts, demonstrating immunogenicity of the DC vaccine. A preliminary analysis of the data indicates no pts achieved an overall objective response, although 4 disease stabilisations were observed at week 12. Conclusions: In this phase I/II study vaccination with lysate-loaded DC, matured or not, was well tolerated. Increased IR to tumor lysate or TAA peptides were observed indicating that lysate-loaded DC may induce anti-tumor immune responses, even in patients with advanced metastatic disease. Further clinical studies will be conducted in patients with less advanced disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IDM S.A.