Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors |
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| Authors: | Ayala Tamir Ernesto Basaglia 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 |
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| Institution: | (1) Department of Immunology, Imperial College at Hammersmith Hospital, London, UK;(2) Liver Surgery Section, Department of Surgical Oncology and Technology, Imperial College at Hammersmith Hospital, London, UK;(3) Department of Radiology, Imperial College at Hammersmith Hospital, London, UK;(4) Department of Histopathology, Faculty of Medicine, Imperial College at Hammersmith Hospital, London, UK;(5) Department of Molecular Biology, King’s College London, Guy’s Hospital Campus, London, UK;(6) Department of Medicine, King’s College London, Guy’s Hospital Campus, London, UK;(7) Immunoregulation Laboratory, Department of Nephrology and Transplantation, Guy’s Hospital, King’s College London, Guy’s King’s and St. Thomas School of Medicine, 5th Floor Thomas Guy House, SE1 9RT London, UK;(8) Present address: Research Department, Puget Sound Blood Center, Seattle, WA 98104, USA |
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| 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.
An erratum to this article can be found at |
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| Keywords: | Dendritic cells Carcinoembryonic antigen (CEA) Immunotherapy |
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