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 microg/dose; n = 7) or anti-Id (500 microg/dose; n = 6) at weeks 0, 2, and 6 in combination with granulocyte macrophage colony-stimulating factor (75 microg/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-gamma-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-gamma- 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.
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 microg/dose; n = 7) or anti-Id (500 microg/dose; n = 6) at weeks 0, 2, and 6 in combination with granulocyte macrophage colony-stimulating factor (75 microg/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-gamma-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-gamma- 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.
Authors: Se Hee Park; Kon-Young Ji; Seo Young Park; Hyun Min Kim; Sang Hoon Ma; Ju Hui Do; Hyuno Kang; Hyung Sik Kang; Doo-Byoung Oh; Jae Sung Shim; Young Hee Joung Journal: Sci Rep Date: 2022-06-13 Impact factor: 4.996
Authors: P Went; M Vasei; L Bubendorf; L Terracciano; L Tornillo; U Riede; J Kononen; R Simon; G Sauter; P A Baeuerle Journal: Br J Cancer Date: 2006-01-16 Impact factor: 7.640
Authors: Joseph P Connor; Mihaela C Cristea; Nancy L Lewis; Lionel D Lewis; Philip B Komarnitsky; Maria R Mattiacci; Mildred Felder; Sarah Stewart; Josephine Harter; Jean Henslee-Downey; Daniel Kramer; Roland Neugebauer; Roger Stupp Journal: BMC Cancer Date: 2013-01-15 Impact factor: 4.430