title: Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study.
abstract: We report on the safety and immunogenicity of idiotypic DNA vaccination in a phase I, non-randomised, open-label study in patients with multiple myeloma. The study used DNA fusion gene vaccines encoding patient-specific single chain variable fragment, or idiotype (Id), linked to fragment C (FrC) of tetanus toxin. Patients in complete or partial response following high-dose chemotherapy and autologous stem cell transplant were vaccinated intramuscularly with 1 mg DNA on six occasions, beginning at least 6 months post-transplant; follow-up was to week 52. Fourteen patients were enrolled on study and completed vaccinations. Idiotypic DNA vaccines were well tolerated with vaccine-related adverse events limited to low-grade constitutional symptoms. FrC- and Id-specific T-cell responses were detected by ex vivo ELISPOT in 9/14 and 3/14 patients, respectively. A boost of pre-existing anti-FrC antibody (Ab) was detected by ELISA in 8/14 patients, whilst anti-Id Ab was generated in 1/13 patients. Overall, four patients (29 %) made an immune response to FrC and Id, with six patients (43 %) responding to FrC alone. Over the 52-week study period, serum paraprotein was undetectable, decreased or remained stable for ten patients (71 %), whilst ongoing CR/PR was maintained for 11 patients (79 %). The median time to progression was 38.0 months for 13/14 patients. Overall survival was 64 % after a median follow-up of 85.6 months.
authors.affiliation: Experimental Cancer Medicine Centre Southampton and Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Somers Cancer Research Building, Mailpoint 824, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK, kjm8@soton.ac.uk.
authors.forename: Katy J
authors.initials: KJ
authors.lastname: McCann
authors.forename: Rosemary
authors.initials: R
authors.lastname: Godeseth
authors.forename: Lindsey
authors.initials: L
authors.lastname: Chudley
authors.forename: Ann
authors.initials: A
authors.lastname: Mander
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Di Genova
authors.forename: Paul
authors.initials: P
authors.lastname: Lloyd-Evans
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Kerr
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Malykh
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Jenner
authors.forename: Kim H
authors.initials: KH
authors.lastname: Orchard
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
authors.forename: Christian H
authors.initials: CH
authors.lastname: Ottensmeier
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D056724:Immunity, Humoral; D007130:Immunoglobulin Idiotypes / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000235:genetics; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D019444:Vaccines, DNA; C040635:tetanus toxin fragment C