Poor ex vivo induction of T-cell responses to idiotype or tumor cell lysate-pulsed autologous dendritic cells in advanced pre-treated multiple myeloma.
This study evaluated the feasibility of using dendritic cells (DCs) to generate, ex vivo, anti-tumor cytotoxic T lymphocytes (CTL) in patients with stage III multiple myeloma (MM). Nucleated cells from eight patients who had received chemotherapy (three of whom had undergone autologous hemopoeitic stem cell transplantation) were collected by apheresis. Their monocytes were enriched using counter-current centrifugation, differentiated into DCs which were further co-cultured with autologous CD8 lymphocytes to induce CTL. The DCs were pulsed either with the idiotypic paraprotein (regarded as a tumor-specific antigen) or with autologous MM cell lysate before co-culture. Specific T-cell responses were measured in IFNgamma enzyme-linked immunospot and chromium release assays of autologous plasmocyte targets. A slight increase in IFNgamma secretion by T-cells was observed for two patients (DCs pulsed with idiotypic paraprotein for one, MM cell lysate for the other). No or weak specific lysis of plasmocyte targets was observed in the chromium release assays. In conclusion, the T-cell response to pulsed DCs was very weak or absent. There are clinical and technical reasons that could explain, in part, this lack of response.
Garderet
Laurent
L
Inserm and EA1638, Faculté de Médecine Saint Antoine, Université Pierre et Marie Curie (Paris 6), Paris, France.
Mazurier
Christelle
C
Pellat-Deceunynck
Catherine
C
Karim
Abdul
A
Baudin
Bruno
B
Funck-Brentano
Christian
C
Bouchet
Sandrine
S
Geffroy
Alexandrine
A
Bataille
Régis
R
Gorin
Norbert-Claude
NC
Lopez
Manuel
M
D000328:Adult; D000368:Aged; D001781:Blood Component Removal; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000379:methods*; D002857:Chromium / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D007130:Immunoglobulin Idiotypes; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007130:Immunoglobulin Idiotypes; D014409:Tumor Necrosis Factor-alpha; D002857:Chromium