Dendritic cells transfected with allo-tumor mRNA as cancer vaccine in treatment of hormone resistant prostate cancer patients

Abstract

2541 Background: In this phase I/II trial, patients with hormone resistant prostate cancer and increasing PSA were vaccinated with autologous monocyte-derived dendritic cells (DCs) that have been transfected with mRNA from three prostate cancer cell lines (DU145, LNCaP and PC-3). By this strategy, we intend to make the DCs present a broad spectrum of tumor-associated antigens and elicit an immune response against tumor-associated proteins shared between the selected tumor cell lines and the individual patient. Methods: Twenty patients all with increasing PSA levels were included. Each patient received at least four weekly injections with 2x107 transfected DC. Ten patients had their DCs injected intranodally under ultrasonic guidance while 9 patients received the DCs intradermally. Safety and feasibility were evaluated, secondary end points were immune monitoring and PSA response. Immune responses were measured as DTH and by vitro immunoassays including ELISPOT, T cell proliferation test and cytotoxicity test in pre- and post-vaccination peripheral blood samples. Results: No grade II-IV toxicity and no serious adverse events were observed. Twelve patients developed a specific immune response to tumor mRNA transfected dendritic cells. In one patient HLA-A9 restricted CTL’s were generated that specifically killed an HLA-9 expressing prostate cancer cell line. Seven patients obtained stable disease by PSA evaluation (lPSA<50 % decrease and PSA< 25% increase). Ten patients showed a significant decrease in log slope PSA. Patients with lower PSA levels at inclusion had a better immunological response. Intranodal injection did not improve the results compared to intradermal vaccination. Conclusion: We conclude that our strategy of vaccinating with mRNA transfected DCs results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level, suggest that this approach might become potential useful as a treatment modality for prostate cancer patients. No significant financial relationships to disclose.