Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma.
BACKGROUND
We previously demonstrated that dendritic cell-based immunotherapy induced protective antitumor immunity with a prolonged survival rate in mice. However, the clinical relevance is still in question. To examine this, we designed a clinical trial using chemotherapy followed by antigen-pulsed dendritic cell vaccination in mesothelioma patients.


OBJECTIVE
The aim of this study was to assess the safety and immunological response induced by the administration of tumor lysate-pulsed dendritic cells in patients with mesothelioma.


METHODS
Ten patients with malignant pleural mesothelioma received three vaccinations of clinical-grade autologous dendritic cells intradermally and intravenously at 2-week intervals after chemotherapy. Each vaccine was composed of 50 x 10(6) mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH) as surrogate marker. Delayed-type hypersensitivity activity to tumor antigens and KLH was assessed, both in vivo and in vitro. Peripheral blood mononuclear cells during the treatment were analyzed for immunological responses.


RESULTS
Administration of dendritic cells pulsed with autologous tumor lysate in patients with mesothelioma was safe with moderate fever as the only side effect. There were no grade 3 or 4 toxicities associated with the vaccines or any evidence of autoimmunity. Local accumulations of infiltrating T cells were found at the site of vaccination. The vaccinations induced distinct immunological responses to KLH, both in vitro and in vivo. Importantly, after three vaccinations, cytotoxic activity against autologous tumor cells was detected in a subgroup of patients.


CONCLUSIONS
This study demonstrated that autologous tumor lysate-pulsed dendritic cell-based therapy is feasible, well-tolerated, and capable of inducing immunological response to tumor cells in mesothelioma patients. Clinical trial registered with www.clinicaltrials.gov (NCT00280982).
Hegmans
Joost P
JP
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
Veltman
Joris D
JD
Lambers
Margaretha E
ME
de Vries
I Jolanda M
IJ
Figdor
Carl G
CG
Hendriks
Rudi W
RW
Hoogsteden
Henk C
HC
Lambrecht
Bart N
BN
Aerts
Joachim G
JG
D000368:Aged; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005240:Feasibility Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008654:Mesothelioma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000276:immunology / Q000628:therapy*