Dendritic Cells Pulsed with an Anti-Idiotype Antibody Mimicking Carcinoembryonic Antigen (CEA) Can Reverse Immunological Tolerance to CEA and Induce Antitumor Immunity in CEA Transgenic Mice
- 15 July 2004
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 64 (14), 4995-5003
- https://doi.org/10.1158/0008-5472.can-04-0626
Abstract
In this report, we have studied the immunogenicity of the nominal antigen, carcinoembryonic antigen (CEA), and that of an anti-idiotype antibody, 3H1, which mimics CEA and can be used as a surrogate for CEA. We have demonstrated that immunization of CEA transgenic mice with bone marrow-derived mature dendritic cells (DC) loaded with anti-idiotype 3H1 or CEA could reverse CEA unresponsiveness and result in the induction of CEA-specific immune responses and the rejection of CEA-transfected MC-38 colon carcinoma cells, C15. Immunized mice splenocytes proliferated in an antigen-specific manner by a mechanism dependent on the functions of CD4, MHC II, B7–2, CD40, CD28, and CD25. However, immune splenic lymphocytes isolated from 3H1-DC-vaccinated mice when stimulated in vitro with 3H1 or CEA secreted significantly higher levels of Th1 cytokines than did CEA-DC vaccinated mice. DC vaccination also induced antigen-specific effector CD8+ T cells capable of expressing interluekin-2, IFN-γ, and tumor necrosis factor (TNF)-α and displayed cytotoxic activity against C15 cells in an MHC class I-restricted manner. 3H1-DC vaccination resulted in augmented CTL responses and the elevated expression of CD69, CD25, and CD28 on CD8+ CTLs. The immune responses developed in 3H1-DC-immunized mice resulted in rejection of C15 tumor cells in nearly 100% of experimental mice, whereas only 40% of experimental mice immunized with CEA-DC were protected from C15 tumor growth. These findings suggest that under the experimental conditions used, 3H1-DC vaccination was better than CEA-DC vaccination in breaking immune tolerance to CEA and inducing protective antitumor immune responses in this murine model transgenic for human CEA.Keywords
This publication has 19 references indexed in Scilit:
- Immunotherapy with Autologous, Human Dendritic Cells Transfected with Carcinoembryonic Antigen mRNACancer Investigation, 2003
- An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic miceVaccine, 2001
- Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapyProceedings of the National Academy of Sciences of the United States of America, 2001
- DNA Vaccines: Immunology, Application, and OptimizationAnnual Review of Immunology, 2000
- Immunobiology of Dendritic CellsAnnual Review of Immunology, 2000
- Immunotherapy of cancer with dendritic-cell-based vaccinesCancer Immunology, Immunotherapy, 1998
- Origin, maturation and antigen presenting function of dendritic cellsCurrent Opinion in Immunology, 1997
- Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.The Journal of Experimental Medicine, 1996
- CD40 ligand-transduced co-stimulation of T cells in the development of helper functionNature, 1995
- Carcinoembryonic antigen gene family: Molecular biology and clinical perspectivesJournal of Clinical Laboratory Analysis, 1991