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Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Objective

Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population.

Materials and methods

The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively.

Results

No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p < 0.0018). Twelve patients who continued immunotherapy with the second cycle had a median PSADT of 58 months that remained stable after the second cycle. In the peripheral blood, specific PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment.

Summary

Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

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Abbreviations

AEs:

Adverse events

BCR:

Biochemical relapse

CTL:

Cytotoxic T lymphocytes

DCs:

Dendritic cells

DCVAC/PCa:

Dendritic cells pulsed with the killed prostate-cancer cell line LNCaP

GMP:

Good manufacturing practice

LNCaP:

Androgen-sensitive human prostate adenocarcinoma cells

NKs:

Natural killer cells

PBMCs:

Peripheral blood mononuclear cells

PCa:

Prostate cancer

PSA:

Prostate-specific antigen

PSADT :

PSA doubling time

RP:

Radical prostatectomy

RT:

Radiotherapy

SAEs:

Serious adverse events

s.c.:

Subcutaneously

SRT:

Salvage radiotherapy

Tregs:

Regulatory T cells

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Acknowledgements

The work of the Department of Immunology of Charles University is supported by the Ministry of Health, Czech Republic-Conceptual Development of Research Organization (University Hospital Motol, Prague, Czech Republic, 00064203) and Grant AZV ČR (agency for medical research, Czech Republic) 16-28135A.

Author information

Author notes

  1. Jitka Fucikova, Michal Podrazil, Radek Spisek and Jirina Bartunkova contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, V Uvalu 84, Prague 5, 15005, Prague, Czech Republic

    Jitka Fucikova, Michal Podrazil, Jana Kayserova, Rudolf Horvath, Katerina Vavrova, Radek Spisek & Jirina Bartunkova

  2. Sotio, Prague, Czech Republic

    Jitka Fucikova, Pavla Bilkova, Michal Hensler, Anna Fialova, Klara Sochorova, Daniela Rozkova, Radek Spisek & Jirina Bartunkova

  3. Department of Urology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

    Ladislav Jarolim

  4. Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    Zdenka Gasova

  5. Laboratory ‘Cancer, Immune Control and Escape’, INSERM U1138, Cordeliers Research Centre, Paris, France

    Etienne Becht

  6. UMRS 1138, University Pierre and Marie Curie, Paris, France

    Etienne Becht

  7. UMRS 1138, University Paris Descartes, Paris, France

    Etienne Becht

  8. Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

    Jana Klouckova

  9. Department of Pediatric and Adult Rheumatology, University Hospital Motol, Prague, Czech Republic

    Rudolf Horvath

Authors
  1. Jitka Fucikova
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  2. Michal Podrazil
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Corresponding author

Correspondence to Jirina Bartunkova.

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Conflict of interest

Jitka Fucikova, Michal Podrazil, Pavla Bilkova, Michal Hensler, Anna Fialova, Klara Sochorova, Daniela Rozkova are part-time employees of Sotio; Jirina Bartunkova and Radek Spisek are minority shareholders of Sotio. The other authors declare that they have no conflict of interest.

Informed consent

Written informed consent was obtained from all patients before any of the study procedures was conducted.

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Fucikova, J., Podrazil, M., Jarolim, L. et al. Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer. Cancer Immunol Immunother 67, 89–100 (2018). https://doi.org/10.1007/s00262-017-2068-x

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  • DOI: https://doi.org/10.1007/s00262-017-2068-x

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