T-cell receptor BV gene usage in colorectal carcinoma patients immunised with recombinant Ep-CAM protein or anti-idiotypic antibody
| Autor: | Shahryar Kiaii, Mahmood Jeddi-Tehrani, Jan-Erik Frödin, Mohammad-Reza Rezvany, Szilvia Mosolits, Jan Fagerberg, Katja Markovic, Håkan Mellstedt |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_treatment Immunology Immune system Antigen Antigens Neoplasm medicine Immunology and Allergy Humans Aged Vaccines Synthetic Polymorphism Genetic biology business.industry ELISPOT T-cell receptor Middle Aged Epithelial Cell Adhesion Molecule Complementarity Determining Regions Antibodies Anti-Idiotypic Cytokine Oncology Genes T-Cell Receptor beta biology.protein Female Immunization Antibody business Colorectal Neoplasms Adjuvant Cell Adhesion Molecules CD8 |
| Zdroj: | Cancer immunology, immunotherapy : CII. 54(6) |
| ISSN: | 0340-7004 |
| Popis: | The tumour-associated antigen, Ep-CAM, is over-expressed in colorectal carcinoma (CRC). In the present study, a recombinant Ep-CAM protein or a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM, either alone or in combination, was used for vaccination of CRC patients (n=9). GM-CSF was given as an adjuvant cytokine. A cellular immune response was assessed by measuring anti-Ep-CAM lymphoproliferation, IFN-gamma production (ELISPOT) and by analysing the TCR BV gene usage within the CD4+ and CD8+ T-cell subsets followed by CDR3 fragment analysis. A proliferative and/or IFN-gamma T-cell response was induced against the Ep-CAM protein in eight out of nine patients, and against Ep-CAM-derived peptides in nine out of nine patients. Analysis of the TCR BV gene usage showed a significantly higher usage of BV12 family in CD4+ T cells of patients both before and after immunisation than in those of healthy control donors (p0.05). In the CD8+ T-cell subset, a significant (p0.05) increase in the BV19 usage was noted in patients after immunisation. In individual patients, a number of TCR BV gene families in both CD4+ and CD8+ T cells were over-expressed mainly in post-immunisation samples. Analysis of the CDR3 length polymorphism revealed a higher degree of clonality in post-immunisation samples than in pre-immunisation samples. In vitro stimulation with Ep-CAM protein confirmed the expansion of anti-Ep-CAM T-cell clones. The results indicate that immunisation with the Ep-CAM protein and/or anti-Id entails the induction of an anti-Ep-CAM T-cell response in CRC patients, and suggest that BV19+ CD8+ T cells might be involved in a vaccine-induced immune response. |
| Databáze: | OpenAIRE |
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