2007
Vaccination of myeloma patients with monoclonal immunoglobulin loaded dendritic cells: preclinical and first clinical results of a phase I/II clinical trial.
OČADLÍKOVÁ, Darina, Lenka ZAHRADOVÁ, Lucie KOVÁŘOVÁ, Jaroslav MICHÁLEK, Roman HÁJEK et. al.Základní údaje
Originální název
Vaccination of myeloma patients with monoclonal immunoglobulin loaded dendritic cells: preclinical and first clinical results of a phase I/II clinical trial.
Název česky
Vakcinace pacientů s mnohočetným myelomem dendritickými buňkami loadovanými monoklonálním imunoglobulinem: preklinické a první klinické výsledky klinické studie fáze I/II.
Autoři
OČADLÍKOVÁ, Darina (203 Česká republika, garant), Lenka ZAHRADOVÁ (203 Česká republika), Lucie KOVÁŘOVÁ (203 Česká republika), Jaroslav MICHÁLEK (203 Česká republika) a Roman HÁJEK (203 Česká republika)
Vydání
Blood reviews, 2007
Další údaje
Jazyk
angličtina
Typ výsledku
Konferenční abstrakt
Obor
30200 3.2 Clinical medicine
Stát vydavatele
Maďarsko
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 10.896
Kód RIV
RIV/00216224:14110/07:00019219
Organizační jednotka
Lékařská fakulta
ISSN
UT WoS
000249533100213
Klíčová slova anglicky
Multiple myeloma; Id-protein; Vaccine
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 9. 4. 2010 10:29, Mgr. Darina Očadlíková, Ph.D.
V originále
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.
Česky
Vakcinace pacientů s mnohočetným myelomem dendritickými buňkami loadovanými monoklonálním imunoglobulinem: preklinické a první klinické výsledky klinické studie fáze I/II.
Návaznosti
| NR8945, projekt VaV |
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