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.
OBJECTIVE
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.


METHODS
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.
Immune and Gene Therapy Laboratory, Department of Oncology (Radiumhemmet), Karolinska Institute, Stockholm, Sweden.
Szilvia
S
Mosolits
Katja
K
Markovic
Jan-Erik
JE
Frödin
Lena
L
Virving
Carl G M
CG
Magnusson
Michael
M
Steinitz
Jan
J
Fagerberg
Håkan
H
Mellstedt
D000368:Aged; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000633:toxicity; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000633:toxicity; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D000071858:Epithelial Cell Adhesion Molecule; D000939:Epitopes / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D012004:Rectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D010446:Peptide Fragments