Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study
Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study
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.
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Mccann, Katy J.
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Godeseth, Rosemary
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Chudley, Lindsey
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Mander, Ann
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Di Genova, Gianfranco
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Lloyd-Evans, Paul
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Kerr, Jonathan P.
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Malykh, Vladimir B.
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Jenner, Matthew W.
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Orchard, Kim H
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Stevenson, Freda K.
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Ottensmeier, Christian H.
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August 2015
Mccann, Katy J.
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Godeseth, Rosemary
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Chudley, Lindsey
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Mander, Ann
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Di Genova, Gianfranco
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Lloyd-Evans, Paul
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Kerr, Jonathan P.
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Malykh, Vladimir B.
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Jenner, Matthew W.
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Orchard, Kim H
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Stevenson, Freda K.
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Ottensmeier, Christian H.
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Mccann, Katy J., Godeseth, Rosemary, Chudley, Lindsey, Mander, Ann, Di Genova, Gianfranco, Lloyd-Evans, Paul, Kerr, Jonathan P., Malykh, Vladimir B., Jenner, Matthew W., Orchard, Kim H, Stevenson, Freda K. and Ottensmeier, Christian H.
(2015)
Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study.
Cancer Immunology Immunotherapy, 64 (8), .
(doi:10.1007/s00262-015-1703-7).
(PMID:25982371)
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.
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art%3A10.1007%2Fs00262-015-1703-7.pdf
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Accepted/In Press date: 21 April 2015
e-pub ahead of print date: 16 May 2015
Published date: August 2015
Organisations:
Cancer Sciences
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Local EPrints ID: 396335
URI: http://eprints.soton.ac.uk/id/eprint/396335
ISSN: 0340-7004
PURE UUID: 41fc788b-85da-4fc1-a514-810a31028b8a
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Date deposited: 08 Jun 2016 10:48
Last modified: 15 Mar 2024 02:53
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Contributors
Author:
Katy J. Mccann
Author:
Rosemary Godeseth
Author:
Lindsey Chudley
Author:
Ann Mander
Author:
Gianfranco Di Genova
Author:
Paul Lloyd-Evans
Author:
Jonathan P. Kerr
Author:
Vladimir B. Malykh
Author:
Matthew W. Jenner
Author:
Kim H Orchard
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