Publication details

The preparation of monoclonal immunoglobulin loaded dendritic cells vaccine for myeloma patients under GMP conditions: preclinical and first clinical results of a phase I/II clinical trial.

Authors

OČADLÍKOVÁ Darina ZAHRADOVÁ Lenka KOVÁŘOVÁ Lucie MICHÁLEK Jaroslav HÁJEK Roman

Year of publication 2007
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description Feasibility and safety of vaccination with Id-protein loaded autologous dendritic cells was proved in patients with multiple myeloma under the GMP conditions. 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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