Induction of p53-Specific Immunity by a p53 Synthetic Long Peptide Vaccine in Patients Treated for Metastatic Colorectal Cancer

Purpose: The tumor-associated self-antigen p53 is commonly overexpressed in cancer, including colorectal cancer, and can serve as a target for immunotherapy. The safety and immunogenicity of a p53 synthetic long peptide (p53-SLP) vaccine were investigated in patients treated for metastatic colorecta...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical cancer research Vol. 15; no. 3; pp. 1086 - 1095
Main Authors:	SPEETJENS, Frank M, KUPPEN, PeterJ. K, DRIJFHOUT, Jan W, VAN DE VELDE, Cornelis J. H, MELIEF, Cornelis J. M, VAN DER BURG, Sjoerd H, WELTERS, MarijJ. P, ESSAHSAH, Farah, VOET VAN DEN BRINK, Anne Marie E. G, KALLENBERG LANTRUA, M. Graziella, VALENTIJN, A. Rob P. M, OOSTENDORP, Jaap, FATHERS, Lorraine M, NIJMAN, Hans W
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-02-2009
Subjects:	Aged Antineoplastic agents Biological and medical sciences Cancer Vaccines - adverse effects Cancer Vaccines - immunology Cancer Vaccines - therapeutic use CD4-Positive T-Lymphocytes - immunology colorectal cancer Colorectal Neoplasms - immunology Colorectal Neoplasms - pathology Colorectal Neoplasms - therapy Cytokines - biosynthesis Female Gastroenterology. Liver. Pancreas. Abdomen Humans immunomonitoring immunotherapy Male Medical sciences Middle Aged Neoplasm Metastasis p53 Pharmacology. Drug treatments Stomach. Duodenum. Small intestine. Colon. Rectum. Anus T-Lymphocytes, Cytotoxic - immunology Tumor Suppressor Protein p53 - adverse effects Tumor Suppressor Protein p53 - immunology Tumor Suppressor Protein p53 - therapeutic use Tumors vaccine Vaccines, Subunit - adverse effects Vaccines, Subunit - immunology Vaccines, Subunit - therapeutic use Human Rectal disease Acquired immunity Peptides Induction Colorectal cancer Patient Vaccine Malignant tumor Metastasis Colonic disease TP53 Gene Synthetic product Treatment Digestive diseases Intestinal disease Advanced stage Cancer Tumor suppressor gene
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Purpose: The tumor-associated self-antigen p53 is commonly overexpressed in cancer, including colorectal cancer, and can serve as a target for immunotherapy. The safety and immunogenicity of a p53 synthetic long peptide (p53-SLP) vaccine were investigated in patients treated for metastatic colorectal cancer. Experimental Design: Ten patients were vaccinated twice with a set of 10 overlapping p53-SLP in a phase I/II trial. Both the safety and the breadth, magnitude, and polarization of vaccine-induced p53-specific T cells was evaluated in blood samples drawn before and after vaccination by IFN-γ enzyme-linked immunospot, proliferation, cytokine secretion, and multiparameter flow cytometry. The migratory capacity of p53-specific T cells was evaluated by assessing their presence in a biopsy of the second vaccination site. Results: Toxicity was limited to grade 1/2, mostly at the vaccination site. p53-specific T-cell responses were induced in 9 of 10 colorectal cancer patients as measured by IFN-γ enzyme-linked immunospot, proliferation, and cytokine bead array. In 6 of 9 tested patients, p53-specific T-cell reactivity persisted at least 6 months. Furthermore, p53-specific T cells isolated from the vaccination site were characterized as CD4 + T cells producing both T-helper types 1 and 2 cytokines on stimulation with p53 peptide and p53 protein. Multiparameter flow cytometry revealed that only a minor population of the p53-specific CD4 + T cells was optimally polarized. Conclusions: The p53-SLP vaccine is safe and capable to induce p53-specific T-cell responses in patients treated for colorectal cancer. New trials should focus on improving the polarization of the p53-SLP vaccine-induced T-cell response.
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.CCR-08-2227