a 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.

Basic information

Original name

Vaccination of myeloma patients with monoclonal immunoglobulin loaded dendritic cells: preclinical and first clinical results of a phase I/II clinical trial.

Name in Czech

Vakcinace pacientů s mnohočetným myelomem dendritickými buňkami loadovanými monoklonálním imunoglobulinem: preklinické a první klinické výsledky klinické studie fáze I/II.

Authors

OČADLÍKOVÁ, Darina (203 Czech Republic, guarantor), Lenka ZAHRADOVÁ (203 Czech Republic), Lucie KOVÁŘOVÁ (203 Czech Republic), Jaroslav MICHÁLEK (203 Czech Republic) and Roman HÁJEK (203 Czech Republic)

Edition

Cellular Therapy. 2007

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30200 3.2 Clinical medicine

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 10.896

RIV identification code

RIV/00216224:14110/07:00023887

Organization unit

Faculty of Medicine

ISSN

UT WoS

000249533100213

Keywords in English

Multiple myeloma; Id-protein; vaccine

Tags

International impact, Reviewed
Změněno: 9/4/2010 10:26, Mgr. Darina Očadlíková, Ph.D.

Abstract

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.

In Czech

Vakcinace pacientů s mnohočetným myelomem dendritickými buňkami loadovanými monoklonálním imunoglobulinem: preklinické a první klinické výsledky klinické studie fáze I/II.

Links

LC06027, research and development project
Name: Univerzitní výzkumné centrum - Česká myelomová skupina (Acronym: LC MGUS)
Investor: Ministry of Education, Youth and Sports of the CR, University Research Centre - Czech Myeloma Group