Personalized peptide vaccination for advanced biliary tract cancer: IL-6, nutritional status and pre-existing antigen-specific immunity as possible biomarkers for patient prognosis

Yoshitomi,Munehiro; Yutani,Shigeru; Matsueda,Satoko; Ioji,Tetsuya; Komatsu,Nobukazu; Shichijo,Shigeki; Yamada,Akira; Itoh,Kyogo; Sasada,Tetsuro; Kinoshita,Hisafumi

doi:10.3892/etm.2011.424

March 2012 Volume 3 Issue 3

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March 2012 Volume 3 Issue 3

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Article

Personalized peptide vaccination for advanced biliary tract cancer: IL-6, nutritional status and pre-existing antigen-specific immunity as possible biomarkers for patient prognosis

Authors:
- Munehiro Yoshitomi
- Shigeru Yutani
- Satoko Matsueda
- Tetsuya Ioji
- Nobukazu Komatsu
- Shigeki Shichijo
- Akira Yamada
- Kyogo Itoh
- Tetsuro Sasada
- Hisafumi Kinoshita
View Affiliations / Copyright

Affiliations: Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan, Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan, Cancer Vaccine Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Fukuoka, Japan
Pages: 463-469
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Published online on: December 20, 2011

https://doi.org/10.3892/etm.2011.424
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Abstract

Considering that the prognosis of patients with advanced biliary tract cancer (BTC) remains very poor, with a median survival of less than 1 year, new therapeutic approaches need to be developed. In the present study, a phase II clinical trial of personalized peptide vaccination (PPV) was conducted in advanced BTC patients to evaluate the feasibility of this treatment and to identify potential biomarkers. A maximum of 4 human leukocyte antigen-matched peptides, which were selected based on the pre-existing host immunity prior to vaccination, were subcutaneously administered (weekly for 6 consecutive weeks and bi-weekly thereafter) to 25 advanced BTC patients without severe adverse events. Humoral and/or T cell responses specific to the vaccine antigens were substantially induced in a subset of the vaccinated patients. As shown by multivariate Cox regression analysis, lower interleukin-6 (IL-6) and higher albumin levels prior to vaccination and greater numbers of selected vaccine peptides were significantly favorable factors for overall survival [hazard ratio (HR)=1.123, 95% confidence interval (CI) 1.008‑1.252, P=0.035; HR=0.158, 95% CI 0.029-0.860, P=0.033; HR=0.258, 95% CI 0.098-0.682, P=0.006; respectively]. Based on the safety profile and substantial immune responses to vaccine antigens, PPV could be a promising approach for refractory BTC, although its clinical efficacy remains to be investigated in larger-scale prospective studies. The identified biomarkers are potentially useful for selecting BTC patients who would benefit from PPV.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Personalized peptide vaccination for advanced biliary tract cancer: IL-6, nutritional status and pre-existing antigen-specific immunity as possible biomarkers for patient prognosis

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