Induction of p53-specific Immune Responses in Colorectal Cancer Patients Receiving a Recombinant ALVAC-p53 Candidate Vaccine

• Published in: Clinical cancer research 2002-05, Vol.8 (5), p.1019-1027
• Main Authors: VAN DER BURG, Sjoerd H, MENON, Anand G, MELIEF, Cornelis J. M, REDEKER, Anke, BONNET, Marie-Claude, DRIJFHOUT, Jan Wouter, TOLLENAAR, Rob A. E. M, VAN DE VELDE, Cornelis J. H, MOINGEON, Philippe, KUPPEN, Peter J. K, OFFRINGA, Rienk
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibody Formation; Antineoplastic agents; Biological and medical sciences; Canarypox virus - genetics; Cancer Vaccines - genetics; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - immunology; Female; Humans; Immunoglobulin G - blood; Immunoglobulin G - drug effects; Immunoglobulin M - blood; Immunoglobulin M - drug effects; Immunotherapy; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Treatment Outcome; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - immunology; Tumor Suppressor Protein p53 - therapeutic use; Vaccination
• ISSN: 1078-0432; 1557-3265

Purpose: The tumor-associated auto-antigen p53 is commonly overexpressed in various types of human cancer, including colorectal cancer. Experiments in preclinical models have shown that it can serve as a target for T-cell-mediated tumor-eradication. The feasibility of a p53-specific therapeutic vaccination was investigated in cancer patients. Experimental Design: A Phase I/II dose-escalation study was performed that evaluated the effect of a recombinant canarypoxvirus (ALVAC) vaccine encoding wild-type human p53 in 15 patients with advanced colorectal cancer. Each group of five patients received three i.v. doses of one-tenth of a dose, one-third of a dose, or 1 dose of the vaccine [1 dose = 1 × 10 7.5 cell culture infectious dosis (CCID) 50 ]. Results: Potent T-cell and IgG antibody responses against the vector component of the ALVAC vaccine were induced in the majority of the patients. Enzyme-linked immunosorbent-spot assay (ELISPOT) analysis of vaccine-induced immunity revealed the presence of IFN-γ-secreting T cells against both ALVAC and p53, whereas no significant interleukin-4 responses were detected. Vaccine-mediated enhancement of p53-specific T-cell immunity was found in two patients in the highest-vaccine-dose group. Conclusions: This study demonstrated the feasibility, even in patients with advanced cancer, to elicit immune responses against the ubiquitously expressed tumor-associated auto-antigen p53. Our results form the basis for additional studies that will explore the antitumor capacity of p53 containing multivalent vaccines in cancer patients with limited tumor burden.