Phase I/II clinical trial of sequential subcutaneous and intravenous delivery of dendritic cell vaccination for refractory multiple myeloma using patient-specific tumour idiotype protein or idiotype (VDJ)-derived class I-restricted peptides.
Fifteen multiple myeloma (MM) patients who had failed maintenance therapy after tandem autologous stem cell transplantation underwent anti-idiotype (Id) vaccination with dendritic cells (DCs). CD14(+)-derived DCs were loaded with the autologous Id as whole protein (=6) or Id-derived class I-restricted peptides (=9) and keyhole limpet hemocyanin (KLH). Vaccination consisted of three subcutaneous (sc) and two intravenous injections of increasing DC doses at 2 weeks interval. DC therapy was well tolerated. Most patients developed both humoral and T-cell responses to KLH, suggesting immunocompetence. Eight of 15 patients developed an Id-specific T-cell proliferative response, 8/15 increased interferon-gamma-secreting T cells and 4/15 showed an Id-positive delayed-type hypersensitivity test. Anti-Id cytotoxic T-lymphocyte precursors increased after DC vaccination in 2/2 evaluable patients. A more robust T-cell response was observed after sc DC injections and increased Id-specific T-cell proliferation was found up to 1 year after vaccination. VDJ-derived peptides were as effective as the whole protein in stimulating T-cell responses. Clinically, 7/15 patients have stable disease after a median follow-up of 26 months, one patient achieved durable partial remission after 40 months, and seven patients progressed. In conclusion, sc injections of cryopreserved Id-pulsed DCs were safe and, in contrast with intravenous administrations, induced anti-MM T-cell responses.
Curti
Antonio
A
Institute of Haematology and Medical Oncology 'L. & A. Seràgnoli', University of Bologna, Bologna, Italy.
Tosi
Patrizia
P
Comoli
Patrizia
P
Terragna
Carolina
C
Ferri
Elisa
E
Cellini
Claudia
C
Massaia
Massimo
M
D'Addio
Alessandra
A
Giudice
Valeria
V
Di Bello
Cristiana
C
Cavo
Michele
M
Conte
Roberto
R
Gugliotta
Gabriele
G
Baccarani
Michele
M
Lemoli
Roberto M
RM
D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000637:transplantation*; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007133:Immunoglobulin Joining Region / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects / Q000379:methods
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin