Vaccination with Ep-CAM Protein or Anti-Idiotypic Antibody Induces Th1-Biased Response against MHC Class I- and II-Restricted Ep-CAM Epitopes in Colorectal Carcinoma Patients

• Published in: Clinical cancer research 2004-08, Vol.10 (16), p.5391-5402
• Main Authors: MOSOLITS, Szilvia, MARKOVIC, Katja, FRÖDIN, Jan-Erik, VIRVING, Lena, MAGNUSSON, Carl G. M, STEINITZ, Michael, FAGERBERG, Jan, MELLSTEDT, Hakan
• Format: Article
• Language: English
• Subjects: Aged; Amino Acid Sequence; Antigens, Neoplasm - immunology; Antigens, Neoplasm - toxicity; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - toxicity; Colonic Neoplasms - immunology; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Epithelial Cell Adhesion Molecule; Epitopes - immunology; Female; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class II - immunology; Humans; Immunoglobulin G - blood; Male; Medical sciences; Molecular Sequence Data; Neoplasm Staging; Peptide Fragments - chemistry; Peptide Fragments - immunology; Pharmacology. Drug treatments; Rectal Neoplasms - immunology; Rectal Neoplasms - pathology; Rectal Neoplasms - therapy; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0425

Purpose: The tumor-associated antigen Ep-CAM (epithelial cell adhesion molecule) is overexpressed in colorectal carcinoma (CRC). The aim of the present study was to evaluate and compare the safety and immunogenicity of a recombinant Ep-CAM protein and a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM. Experimental Design: Patients with resected American Joint Committee on Cancer stages II–IV CRC without remaining macroscopic disease received intradermal/subcutaneous injections of Ep-CAM (400 μg/dose; n = 7) or anti-Id (500 μg/dose; n = 6) at weeks 0, 2, and 6 in combination with granulocyte macrophage colony-stimulating factor (75 μg/day, for 4 consecutive days). Results: Adverse reactions were mild (grade I–II). All patients immunized with the Ep-CAM protein produced Ep-CAM–specific IgG antibodies, predominantly IgG1 and IgG3 subclasses, whereas no humoral response was induced by the anti-Id vaccine. All patients, with one exception in each group, mounted an Ep-CAM–specific proliferative T-cell response. The immune response was more rapid, potent, and protracted after Ep-CAM in comparison with anti-Id vaccination. Interferon-γ-secreting cells (ELISPOT) were detected in both immunization groups against the Ep-CAM protein as well as various Ep-CAM–derived MHC class I- and II-restricted peptides. Flow cytometry analysis showed that Ep-CAM–specific interferon-γ- and perforin-producing cells predominantly resided within CD8 + CD56 − and CD8 dim CD56 + T cells. Conclusions: Ep-CAM protein in combination with granulocyte macrophage colony-stimulating factor induced a long-lasting, Th1-biased humoral and cellular immune response compared with anti-Id. Ep-CAM–specific T cells and natural killer-like T cells responding in a MHC class I- and II-restricted manner were also induced. Vaccination with Ep-CAM protein may warrant further investigation as a novel therapeutic approach to CRC.