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

• 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
• DOI: 10.1158/1078-0432.CCR-08-2227
• EISSN: 1557-3265
• ISSN: 1078-0432

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.