Cancer immunotherapy
Tuck was kind enough to link to an article in the latest issue of The Scientist discussing recent progress in Cancer Immunotherapy.
Message 20332228
One of the persons briefly interviewed in the article works with IDM. There was a reference to a phase II trial conducted by IDM with prostrate cancer patients. This is the abstract relating to this article.
springerlink.metapress.com
Vaccination of prostatectomized prostate cancer patients in biochemical relapse, with autologous dendritic cells pulsed with recombinant human PSA
Benoît Barrou1 Contact Information, Gérard Benoît2, Mahmoud Ouldkaci2, Olivier Cussenot3, Margarita Salcedo4, Sudhanshu Agrawal4, Séverine Massicard4, Nadège Bercovici4, Mats L. Ericson4 Contact Information and Nicolas Thiounn5
(1) Service drsquoUrologie, AP-HP, Hôpital la Pitié-Salpétrière, 47-83 Boulevard de lrsquoHôpital, Cedex 13, 75651 Paris, France
(2) Service drsquoUrologie, AP-HP, Hôpital Kremlin-Bicêtre, Paris, France
(3) Service drsquoUrologie, AP-HP, Hôpital Saint-Louis, Paris, France
(4) Immuno-Designed Molecules, 172 Rue de Charonne, Cedex 11, 75545 Paris, France
(5) Service drsquoUrologie, AP-HP, Hôpital Cochin, Paris, France
Received: 25 May 2003 Accepted: 7 August 2003 Published online: 4 February 2004
Abstract
This study was conducted in prostate cancer patients in biochemical relapse after radical prostatectomy, to assess the feasibility, safety, and immunogenicity of therapeutic vaccination with autologous dendritic cells (DCs) pulsed with human recombinant prostate-specific antigen (PSA) (Dendritophage-rPSA). Twenty-four patients with histologically proven prostate carcinoma and an isolated postoperative rise of serum PSA (>1 ng/ml to 10 ng/ml) after radical prostatectomy were included. The patients received nine administrations of PSA-loaded DCs by combined intravenous, subcutaneous, and intradermal routes over 21 weeks. Postbaseline blood tests were performed at months 1, 3, 6, 9, and 12 (PSA levels), at months 6 and 12 (circulating prostate cancer cells), at month 6 (anti-PSA IgG and IgM antibodies), and at up to eight time points before, during, and after immunization (PSA-specific T cells). Circulating prostate cancer cells detected in six patients at baseline were undetectable at 6 months and remained undetectable at 12 months. Eleven patients had a postbaseline transient PSA decrease on one to three occasions, predominantly occurring at month 1 (7 patients) or month 3 (2 patients). Maximum PSA decrease ranged from 6% to 39%. PSA decrease on at least one occasion was more frequent in patients with low Gleason score (p=0.016) at prostatectomy and with positive skin tests at study baseline (p=0.04). PSA-specific T cells were detected ex vivo by ELISpot for IFN-gamma in 7 patients before vaccination and in 11 patients after vaccination. Of the latter 11 patients, 5 had detectable T cells both before and during the vaccination period, 4 only during the vaccination period, while 2 patients could for technical reasons not be assessed prevaccination. No induction of anti-PSA IgG or IgM antibodies was detected. There were no serious adverse events or otherwise severe toxicities observed during the trial. Immunization with Dendritophage-rPSA was feasible and safe in this cohort of patients. An immune response specific for PSA could be detected in some patients. A notable effect was the disappearance of circulating prostate cells in all patients who were RT-PCR positive before vaccination. |
