Vaccination of myeloma patients with monoclonal immunoglobulin loaded dendritic cells: preclinical and first clinical results of a phase I/II clinical trial.
| Authors | |
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| Year of publication | 2007 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Background: Adjuvant immunotherapy with antigen-loaded dendritic cells (DCs) represents a novel and relatively non-toxic treatment modality for multiple myeloma (MM). Malignant cells in MM produce a monoclonal immunoglobulin (idiotypic protein) which is considered a tumor-specific antigen and can be used for the induction of T lymphocytes. To enhance the anti-myeloma immune response, the idiotypic protein (Id-protein) can be loaded into autologous DCs and used for vaccination. Aims: The aim of this study was to evaluate DC-based vaccine preclinically and test the safety and the immune response of the vaccine in patients with MM. Patients and Methods: Pre-clinical testing was performed in 8 patients with MM. DC loaded with autologous myeloma cells were used for autologous T cell stimulation in vitro. After succesful preclinical testing, we have vaccinated 4 patients with stable disease or asymptomatic slow progressive disease according to EBMT criteria. Patients were pre-treated with high-dose chemotherapy and auto-PBSCT. DC precursors were isolated as an adherent fraction from peripheral blood of the myeloma patients. DCs were prepared in vitro and loaded with Id-protein under GMP conditions as previously described (Ocadlikova et al.Med Oncol 2006, 23: 377-384). Patients were vaccinated every 4 weeks subcutaneously with 6 doses, each containing 1,46-18,1 e 06 (mean 9,52 e 06) DCs. The immune response was evaluated by flow cytometry, Elispot and the skin test of hypersensitivity. Results: IFN-gamma production of T cells stimulated with autologous myeloma cell loaded DC was observed. After successful pre-clinical testing a clinical phase I/II trial was initiated. A total of 24 vaccines were applied to 4 patients so far (January 2007). The viability, number and functional characteristics of in vitro matured DCs loaded with Id-protein were satisfactory with 50,10-99,3% (mean 87,08%) of HLADR/CD86+ cells. Each vaccination was well tolerated with only mild fever in 1 patient. No grade II-IV. toxicity appeared. The clinical trial is ongoing and a total of 12 patients is planned to be evaluated. Conclusions: Vaccination with Id-protein loaded autologous dendritic cells demonstrates feasibility and safety in patients with multiple myeloma pre-treated with high dose chemotherapy. |
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