DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer
DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer
We are evaluating the use of electroporation (EP) to deliver a novel DNA vaccine, p.DOM-PSMA(27). This vaccine encodes a domain (DOM) of fragment C of tetanus toxin to induce CD4(+) T cell help, fused to a tumor-derived epitope from prostate-specific membrane antigen (PSMA) for use in HLA-A2(+) patients with recurrent prostate cancer. We report on safety and tolerability and on antibody response to DOM as a first indication of the effect of EP in patients. In this open label phase I/II, two-arm, dose escalation trial DNA was delivered either by intramuscular injection or by intramuscular injection followed by EP (DNA+EP), with five patients per dose level. Three vaccinations were given at 0, 4, and 8 weeks,with booster doses at 24 and 48 weeks; here we allowed crossover between study arms if supported by the safety and immunological data. In the 20 patients in the first two dose cohorts we observed that beyond brief and acceptable pain at the injection site, EP did not appear to add toxicity to the vaccination. We evaluated humoral responses to DOM. Low anti-DOM IgG antibody responses were observed after intramuscular injection of DNA without EP (at week 12: mean 1.7- vs. 24.5-fold increase over baseline with DNA+EP). These could be boosted by delivery of DNA+EP at later time points. Delivery of DNA+EP at all five vaccinations yielded the highest levels of anti-DOM antibody. Responses persisted to 18 months of follow-up. These data establish EP as a potent method for stimulating humoral responses induced by DNA vaccination in humans.
1269-1278
Low, Lindsey
ec25c30c-369d-4516-b872-4cb3c135c10a
Mander, Ann
2fcb3a33-6bb8-4463-8b06-79cd508e9d80
McCann, Katy
2f58a345-4009-42e5-aa6e-e74d512beae8
Dearnaley, David
9254156f-ba5e-4d15-8522-0f0d00b07584
Tjelle, Torunn
eb43beca-2a55-4216-bf35-ab476f496d87
Mathiesen, Lacob
52f8ce8f-f11a-469f-a09e-68b5f20baeed
Stevenson, Freda
ba803747-c0ac-409f-a9c2-b61fde009f8c
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
2009
Low, Lindsey
ec25c30c-369d-4516-b872-4cb3c135c10a
Mander, Ann
2fcb3a33-6bb8-4463-8b06-79cd508e9d80
McCann, Katy
2f58a345-4009-42e5-aa6e-e74d512beae8
Dearnaley, David
9254156f-ba5e-4d15-8522-0f0d00b07584
Tjelle, Torunn
eb43beca-2a55-4216-bf35-ab476f496d87
Mathiesen, Lacob
52f8ce8f-f11a-469f-a09e-68b5f20baeed
Stevenson, Freda
ba803747-c0ac-409f-a9c2-b61fde009f8c
Ottensmeier, Christian H.
42b8a398-baac-4843-a3d6-056225675797
Low, Lindsey, Mander, Ann, McCann, Katy, Dearnaley, David, Tjelle, Torunn, Mathiesen, Lacob, Stevenson, Freda and Ottensmeier, Christian H.
(2009)
DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer.
Human Gene Therapy, 20 (11), .
(doi:10.1089/hum.2009.067).
Abstract
We are evaluating the use of electroporation (EP) to deliver a novel DNA vaccine, p.DOM-PSMA(27). This vaccine encodes a domain (DOM) of fragment C of tetanus toxin to induce CD4(+) T cell help, fused to a tumor-derived epitope from prostate-specific membrane antigen (PSMA) for use in HLA-A2(+) patients with recurrent prostate cancer. We report on safety and tolerability and on antibody response to DOM as a first indication of the effect of EP in patients. In this open label phase I/II, two-arm, dose escalation trial DNA was delivered either by intramuscular injection or by intramuscular injection followed by EP (DNA+EP), with five patients per dose level. Three vaccinations were given at 0, 4, and 8 weeks,with booster doses at 24 and 48 weeks; here we allowed crossover between study arms if supported by the safety and immunological data. In the 20 patients in the first two dose cohorts we observed that beyond brief and acceptable pain at the injection site, EP did not appear to add toxicity to the vaccination. We evaluated humoral responses to DOM. Low anti-DOM IgG antibody responses were observed after intramuscular injection of DNA without EP (at week 12: mean 1.7- vs. 24.5-fold increase over baseline with DNA+EP). These could be boosted by delivery of DNA+EP at later time points. Delivery of DNA+EP at all five vaccinations yielded the highest levels of anti-DOM antibody. Responses persisted to 18 months of follow-up. These data establish EP as a potent method for stimulating humoral responses induced by DNA vaccination in humans.
This record has no associated files available for download.
More information
Published date: 2009
Identifiers
Local EPrints ID: 73404
URI: http://eprints.soton.ac.uk/id/eprint/73404
ISSN: 1043-0342
PURE UUID: c12553d5-8268-4835-83e9-eef89e5f3489
Catalogue record
Date deposited: 05 Mar 2010
Last modified: 14 Mar 2024 02:40
Export record
Altmetrics
Contributors
Author:
Lindsey Low
Author:
Ann Mander
Author:
Katy McCann
Author:
David Dearnaley
Author:
Torunn Tjelle
Author:
Lacob Mathiesen
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics