Efficient Vaccination of Follicular Lymphoma (FL) Patients with Multiple Intradermal (ID) and Intravenous (IV) Administrations of Mature Dendritic Cells (DC) Loaded with Tumor Cell Lysate Ex Vivo

DCs are the most potent antigen-presenting cells and antigen (Ag) delivery by ex vivo Ag-loaded DC cells may be an effective strategy for FL. The relevant source of tumor Ag, vaccine doses, schedules or routes of administration are still a matter of investigation. Tumor cell lysate (TCL) is an inter...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2005-11, Vol.106 (11), p.1494-1494
Main Authors: Rossi, Jean-Francois, Baudard, Marion, Conge, Anne-Marie, Comte, Frédéric, Costes, Valérie, Veyrunes, Jean-Luc, Quittet, Philippe, Rouillé, Valérie, Barjot, Catherine, Klein, Bernard
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:DCs are the most potent antigen-presenting cells and antigen (Ag) delivery by ex vivo Ag-loaded DC cells may be an effective strategy for FL. The relevant source of tumor Ag, vaccine doses, schedules or routes of administration are still a matter of investigation. Tumor cell lysate (TCL) is an interesting source of multiple tumor Ag. After preclinical study and an acceptation of the “dossier de lot” by the french drug agency (afssaps), we started a phase II study evaluating the feasibility and safety of multiple ID and IV injections of autologous DC-TCL, in 07/04. At this time, 5 FL patients (pts) completed their treatment, with 5 to 7 DC-TCL vaccinations every 2–3 weeks, receiving 5.106 cells IV and 5.106 cells ID per vaccination. All the pts (2F/ 3M, age 44–61; 1 to 8 previous lines of therapy, including autologous transplantion in 2 pts) had measurable disease at inclusion. Tumor lymph node biopsy (for preparing TCL) was followed by rituximab administration in pts with no history of previous infusion of the monoclonal antibody. Cyclophosphamide (2g/m2) and G-CSF (5 mg/kg) were administered to mobilize mononuclear cells including CD14 monocytes. Two pts still had measurable disease at time of vaccination (lymph nodes on CT and Pet scans for the 2 pts, cutaneous localizations and molecular analysis evidence of disease in BM and PB, in 1 pt). Immature DC were obtained from thawed leukapheresis cells cultured for 5 days with GM-CSF and IL-4, pulsed with L, and then induced to mature with TNFalpha and PGE2 for 24 hours. All DC preparations fitted the quality criteria defined by the preclinical study (viability≥60%, ≤20% CD14+ cells, ≥60% CD83+ cells). Vaccinations were safe and well tolerated. One of the 2 pts with prevaccination residual disease entered CR (disappearance of Pet-scan positivity after the 7th vaccination, with sequential Pets, showing an increase of the signal during the first vaccinations linked to an initial lymph node activation), while a PR was observed in the 2nd pt with a regression of both lymph nodes and tumoral subcutaneous lesions. Quantitative PCR for bcl-2 signal were performed in both PB and BM. All pts developed significant delayed-type hypersensitivity responses to DC-TCL (as defined by erythema and induration of more than 5 mm of diameter, lasting 48h at least) after the 4th or 5th vaccinations. Analysis of biopsies performed at the site of DC-TCL injections, showed HSR including neutrophils and dense infiltration by T lymphoc
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V106.11.1494.1494