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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 12/2007

01-12-2007 | Original Article

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

Authors: 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

Published in: Cancer Immunology, Immunotherapy | Issue 12/2007

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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.
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Metadata
Title
Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors
Authors
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
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 12/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-007-0299-y

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