Cancer Immunology, Immunotherapy

, Volume 56, Issue 12, pp 2003–2016 | Cite as

Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors

  • Ayala Tamir
  • Ernesto Basagila
  • Arash Kagahzian
  • Long Jiao
  • Steen Jensen
  • Joanna Nicholls
  • Paul Tate
  • Gordon Stamp
  • Farzin Farzaneh
  • Phillip Harrison
  • Hans Stauss
  • Andrew J. T. George
  • Nagy Habib
  • Robert I. Lechler
  • Giovanna Lombardi
Original Article

Abstract

Background

Dendritic cells (DCs) are the most effective antigen-presenting cells. In the last decade, the use of DCs for immunotherapy of cancer patients has been vastly increased. High endocytic capacity together with a unique capability of initiating primary T-cell responses have made DCs the most potent candidates for this purpose. Although DC vaccination occasionally leads to tumor regression, clinical efficacy, and immunogenicity of DCs in clinical trials has not been yet clarified. The present study evaluated the safety and effectiveness of tumor-lysate loaded DC vaccines in advanced colorectal cancer (CRC) patients with carcinoembryonic antigen (CEA) positive tumors.

Results

Six patients HLA-A*0201-positive were vaccinated with autologous DCs loaded with tumor lysates (TL) together with tetanus toxoid antigen, hepatitis B, and influenza matrix peptides. Two additional patients were injected with DCs that were generated from their sibling or parent with one haplotype mismatch. All patients received the vaccines every 2 weeks, with a total of three intra-nodal injections per patient. The results indicated that DC vaccination was safe and well tolerated by the patients. Specific immune responses were detected and in some patients, transient stabilization or even reduction of CEA levels were observed. The injection of haplotype mismatched HLA-A*0201-positive DCs resulted in some enhancement of the anti-tumor response in vitro and led to stabilization/reduction of CEA levels in the serum, compared to the use of autologous DCs.

Conclusion

Altogether, these results suggest that TL-pulsed DCs may be an effective vaccine method in CRC patients. Elimination of regulatory mechanisms as well as adjustment of the vaccination protocol may improve the efficacy of DC vaccination.

Keywords

Dendritic cells Carcinoembryonic antigen (CEA) Immunotherapy 

Notes

Acknowledgments

This study was supported by the Pedersen Charity Foundation.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Ayala Tamir
    • 1
    • 8
  • Ernesto Basagila
    • 2
  • Arash Kagahzian
    • 2
  • Long Jiao
    • 2
  • Steen Jensen
    • 2
  • Joanna Nicholls
    • 2
  • Paul Tate
    • 3
  • Gordon Stamp
    • 4
  • Farzin Farzaneh
    • 5
  • Phillip Harrison
    • 6
  • Hans Stauss
    • 1
  • Andrew J. T. George
    • 1
  • Nagy Habib
    • 2
  • Robert I. Lechler
    • 7
  • Giovanna Lombardi
    • 7
  1. 1.Department of ImmunologyImperial College at Hammersmith HospitalLondonUK
  2. 2.Liver Surgery Section, Department of Surgical Oncology and TechnologyImperial College at Hammersmith HospitalLondonUK
  3. 3.Department of RadiologyImperial College at Hammersmith HospitalLondonUK
  4. 4.Department of Histopathology, Faculty of MedicineImperial College at Hammersmith HospitalLondonUK
  5. 5.Department of Molecular BiologyKing’s College London, Guy’s Hospital CampusLondonUK
  6. 6.Department of MedicineKing’s College London, Guy’s Hospital CampusLondonUK
  7. 7.Immunoregulation Laboratory, Department of Nephrology and TransplantationGuy’s Hospital, King’s College London, Guy’s King’s and St. Thomas School of MedicineLondonUK
  8. 8.Research DepartmentPuget Sound Blood CenterSeattleUSA

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