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Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA-A2 with a combination of anti-idiotype vaccine and CTL peptides of carcinoembryonic antigen.
Cancer Res. 2007 Mar 15; 67(6):2881-92.CR

Abstract

Induction of potent and sustained antitumor immunity depends on the efficient activation of CD8(+) and CD4(+) T cells. Immunization using dendritic cells loaded with tumor antigens constitute a powerful platform for stimulating cellular immunity. Our previous studies suggested that vaccination with an anti-idiotype antibody 3H1, which mimics a specific epitope of carcinoembryonic antigen (CEA), has the potential to break immune tolerance to CEA and induce anti-CEA antibody as well as CEA-specific CD4(+) T-helper responses in colon cancer patients as well as in mice transgenic for human CEA. Here, we have combined the anti-idiotype 3H1 with the CTL peptides of CEA to augment both T-helper and CTL responses in a clinically relevant mouse model, which is transgenic for both CEA and HLA-A2. We have evaluated the potential of two different HLA-A2-restricted epitopes of CEA pulsed into dendritic cells in a therapeutic setting. The overall immune responses and survival were enhanced in groups of mice immunized with agonist peptide for CEA(691) (YMIGMLVGV)-pulsed dendritic cells or CAP1-6D (YLSGADLNL, agonist peptide for CAP-1)-pulsed dendritic cells. Mice immunized with peptide-pulsed dendritic cells along with 3H1-pulsed dendritic cells resulted in significant increase in survival compared with mice immunized with peptide-pulsed dendritic cells alone (P < 0.02). IFN-gamma ELISPOT and (51)Cr-release assays showed that HLA-A2-restricted, CEA-specific CTL responses were augmented by combined dendritic cell vaccinations. The combined vaccination strategy resulted in increased antigen-specific proliferation of splenocytes and secretion of Th1 cytokines by CD4(+) T cells that correlated with increased survival. These results suggest the potential use of this vaccination strategy for future clinical applications.

Authors+Show Affiliations

Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0509, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17363612

Citation

Saha, Asim, et al. "Therapy of Established Tumors in a Novel Murine Model Transgenic for Human Carcinoembryonic Antigen and HLA-A2 With a Combination of Anti-idiotype Vaccine and CTL Peptides of Carcinoembryonic Antigen." Cancer Research, vol. 67, no. 6, 2007, pp. 2881-92.
Saha A, Chatterjee SK, Foon KA, et al. Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA-A2 with a combination of anti-idiotype vaccine and CTL peptides of carcinoembryonic antigen. Cancer Res. 2007;67(6):2881-92.
Saha, A., Chatterjee, S. K., Foon, K. A., Celis, E., & Bhattacharya-Chatterjee, M. (2007). Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA-A2 with a combination of anti-idiotype vaccine and CTL peptides of carcinoembryonic antigen. Cancer Research, 67(6), 2881-92.
Saha A, et al. Therapy of Established Tumors in a Novel Murine Model Transgenic for Human Carcinoembryonic Antigen and HLA-A2 With a Combination of Anti-idiotype Vaccine and CTL Peptides of Carcinoembryonic Antigen. Cancer Res. 2007 Mar 15;67(6):2881-92. PubMed PMID: 17363612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA-A2 with a combination of anti-idiotype vaccine and CTL peptides of carcinoembryonic antigen. AU - Saha,Asim, AU - Chatterjee,Sunil K, AU - Foon,Kenneth A, AU - Celis,Esteban, AU - Bhattacharya-Chatterjee,Malaya, PY - 2007/3/17/pubmed PY - 2007/4/20/medline PY - 2007/3/17/entrez SP - 2881 EP - 92 JF - Cancer research JO - Cancer Res. VL - 67 IS - 6 N2 - Induction of potent and sustained antitumor immunity depends on the efficient activation of CD8(+) and CD4(+) T cells. Immunization using dendritic cells loaded with tumor antigens constitute a powerful platform for stimulating cellular immunity. Our previous studies suggested that vaccination with an anti-idiotype antibody 3H1, which mimics a specific epitope of carcinoembryonic antigen (CEA), has the potential to break immune tolerance to CEA and induce anti-CEA antibody as well as CEA-specific CD4(+) T-helper responses in colon cancer patients as well as in mice transgenic for human CEA. Here, we have combined the anti-idiotype 3H1 with the CTL peptides of CEA to augment both T-helper and CTL responses in a clinically relevant mouse model, which is transgenic for both CEA and HLA-A2. We have evaluated the potential of two different HLA-A2-restricted epitopes of CEA pulsed into dendritic cells in a therapeutic setting. The overall immune responses and survival were enhanced in groups of mice immunized with agonist peptide for CEA(691) (YMIGMLVGV)-pulsed dendritic cells or CAP1-6D (YLSGADLNL, agonist peptide for CAP-1)-pulsed dendritic cells. Mice immunized with peptide-pulsed dendritic cells along with 3H1-pulsed dendritic cells resulted in significant increase in survival compared with mice immunized with peptide-pulsed dendritic cells alone (P < 0.02). IFN-gamma ELISPOT and (51)Cr-release assays showed that HLA-A2-restricted, CEA-specific CTL responses were augmented by combined dendritic cell vaccinations. The combined vaccination strategy resulted in increased antigen-specific proliferation of splenocytes and secretion of Th1 cytokines by CD4(+) T cells that correlated with increased survival. These results suggest the potential use of this vaccination strategy for future clinical applications. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/17363612/Therapy_of_established_tumors_in_a_novel_murine_model_transgenic_for_human_carcinoembryonic_antigen_and_HLA_A2_with_a_combination_of_anti_idiotype_vaccine_and_CTL_peptides_of_carcinoembryonic_antigen_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=17363612 DB - PRIME DP - Unbound Medicine ER -