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Vaccination of prostatectomized prostate cancer patients in biochemical relapse, with autologous dendritic cells pulsed with recombinant human PSA

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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-γ 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.

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Acknowledgements

We thank Dr Nabi Azar and Dr Françoise Norol for assistance with cell freezing, Dr Brailly for analysis of blood PSA levels, Dr S. Loric for RT-PCR analyses, and F. Vernel Pauillac and I. Hamon for assistance with patient immunomonitoring.

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Authors and Affiliations

  1. Service d’Urologie, AP-HP, Hôpital la Pitié-Salpétrière, 47-83 Boulevard de l’Hôpital, Cedex 13, 75651, Paris, France

    Benoît Barrou

  2. Service d’Urologie, AP-HP, Hôpital Kremlin-Bicêtre, Paris, France

    Gérard Benoît & Mahmoud Ouldkaci

  3. Service d’Urologie, AP-HP, Hôpital Saint-Louis, Paris, France

    Olivier Cussenot

  4. Immuno-Designed Molecules, 172 Rue de Charonne, Cedex 11, 75545, Paris, France

    Margarita Salcedo, Sudhanshu Agrawal, Séverine Massicard, Nadège Bercovici & Mats L. Ericson

  5. Service d’Urologie, AP-HP, Hôpital Cochin, Paris, France

    Nicolas Thiounn

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  1. Benoît Barrou
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  2. Gérard Benoît
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Correspondence to Benoît Barrou.

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Scientific correspondence should be addressed to B. Barrou; editorial correspondence to M.L. Ericson.

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Barrou, B., Benoît, G., Ouldkaci, M. et al. Vaccination of prostatectomized prostate cancer patients in biochemical relapse, with autologous dendritic cells pulsed with recombinant human PSA. Cancer Immunol Immunother 53, 453–460 (2004). https://doi.org/10.1007/s00262-003-0451-2

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  • DOI: https://doi.org/10.1007/s00262-003-0451-2

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