We have performed several clinical studies with dendritic cells in chronic myeloid leukemia and renal cancer, gene-modified tumor cell vaccines for treatment of advanced metastatic renal cancer, lymphoma radioimmunotherapy.
In the field of DNA-vaccination we are optimizing immunogenicity of a vaccine directed against the HER-2 protein overexpressed in breast cancer. We will soon start a clinical trial with genetic engineered T cells expressing a MAGE-A1 specific T cell receptor (developed by the MDC Blankenstein group), and are further developing adoptive T cell therapy with TCR-engineered to recognize B-cell specific antigens and mutated antigens for leukemia and lymphoma therapy.
A pilot clinical study with a gene-modified tumor cell vaccine for treatment of advanced renal cancer has been concluded. A follow-up study with simultaneous administration of an antibody against regulatory T-cells is in preparation. A phase I dendritic cell vaccination study in chronic myeloid leukemia has also been successfully concluded, leading to a multicenter clinical trial in patients with persisting minimal residual disease after imatinib treatment, due to start in 2008.
These clinical studies are flanked by preclinical animal models of DNA vaccination whereby vectors coding for cytokines or the chemokines CCL19 and CCL21 lead to an improved stimulation of antigen-presenting cells / T-cells. With the aim of improving immunity against the adenocarcinoma-associated EpCAM antigen, we have generated mutated, heteroclitic peptides of EpCAM that display high immunogenicity. These peptides are being evaluated for clinical use. A further strategy is T-cell receptor gene transfer for adoptive therapy of Lymphomas. Transgenic T-cells that use the T-cell receptors of EBV-specific CD8 and CD4 T-cell clones are being developed for adoptive immunotherapy of EBV-associated diseases such as Hodgkin’s Disease and Post-Transplant Lymphoproliferative Disorders (PTLDs). Epitopes of the B-cell antigens CD19, CD20 and CD22 are also being evaluated as targets for TCR transgenic T-cells.