+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Identification of CDCA1-derived long peptides bearing both CD4+ and CD8+ T-cell epitopes: CDCA1-specific CD4+ T-cell immunity in cancer patients



Identification of CDCA1-derived long peptides bearing both CD4+ and CD8+ T-cell epitopes: CDCA1-specific CD4+ T-cell immunity in cancer patients



International Journal of Cancer 134(2): 352-366



We recently identified a novel cancer-testis antigen, cell division cycle associated 1 (CDCA1) using genome-wide cDNA microarray analysis, and CDCA1-derived cytotoxic T lymphocyte (CTL)-epitopes. In this study, we attempted to identify CDCA1-derived long peptides (LPs) that induce both CD4+ helper T (Th) cells and CTLs. We combined information from a recently developed computer algorithm predicting HLA class II-binding peptides with CDCA1-derived CTL-epitope sequences presented by HLA-A2 (A*02:01) or HLA-A24 (A*24:02) to select candidate CDCA1-LPs encompassing both Th cell epitopes and CTL-epitopes. We studied the immunogenicity of CDCA1-LPs and the cross-priming potential of LPs bearing CTL-epitopes in both human in vitro and HLA-class I transgenic mice in vivo. Then we analyzed the Th cell response to CDCA1 in head-and-neck cancer (HNC) patients before and after vaccination with a CDCA1-derived CTL-epitope peptide using IFN-γ enzyme-linked immunospot assays. We identified two CDCA1-LPs, CDCA1(39–64)-LP and CDCA1(55–78)-LP, which encompass naturally processed epitopes recognized by Th cells and CTLs. CDCA1-specific CTLs were induced through cross-presentation of CDCA1-LPs in vitro and in vivo. In addition, CDCA1-specific Th cells enhanced induction of CDCA1-specific CTLs. Furthermore, significant frequencies of CDCA1-specific Th cell responses were detected after short-term in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with CDCA1-LPs in HNC patients (CDCA1(39–64)-LP, 74%; CDCA1(55–78)-LP, 68%), but not in healthy donors. These are the first results demonstrating the presence of CDCA1-specific Th cell responses in HNC patients and underline the possible utility of CDCA1-LPs for propagation of both CDCA1-specific Th cells and CTLs.

(PDF emailed within 0-6 h: $19.90)

Accession: 036967611

Download citation: RISBibTeXText

PMID: 24734272

DOI: 10.1002/ijc.28376


Related references

Identification of promiscuous KIF20A long peptides bearing both CD4+ and CD8+ T-cell epitopes: KIF20A-specific CD4+ T-cell immunity in patients with malignant tumor. Clinical Cancer Research 19(16): 4508-4520, 2014

Cancer-associated splicing variants of the CDCA1 and MSMB genes expressed in cancer cell lines and surgically resected gastric cancer tissues. Surgery 145(1): 57-68, 2009

Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination for castration resistant prostate cancer. Cancer Science 108(7): 1452-1457, 2017

Bladder cancer-associated cancer-testis antigen-derived long peptides encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes induced CD4+ T cells expressing converged T-cell receptor genes in vitro. Oncoimmunology 7(4): E1415687-E1415687, 2018

Identification of immunogenic LY6K long peptide encompassing both CD4 + and CD8 + T-cell epitopes and eliciting CD4 + T-cell immunity in patients with malignant disease. Oncoimmunology 3: E28100-E28100, 2014

siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis. Biochemical and Biophysical Research Communications 390(4): 1235-1240, 2010

Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clinical Cancer Research 14(1): 178-187, 2008

Identification of glypican-3-derived long peptides activating both CD8 + and CD4 + T cells; prolonged overall survival in cancer patients with Th cell response. Oncoimmunology 5(1): E1062209-E1062209, 2016

Identification of t cell and b cell epitopes in synthetic peptides derived from a streptococcus mutans protein and characterization of their antigenicity and immunogenicity. Archives of Oral Biology 35(SUPPL): 39S-47S, 1990

Rabies virus-specific T cell hybridomas: identification of class II MHC-restricted T-cell epitopes using synthetic peptides. Hybridoma 8(3): 263-275, 1989

Identification of multiple T cell epitopes on Bet v I, the major birch pollen allergen, using specific T cell clones and overlapping peptides. Journal of Immunology 150(3): 1047-1054, 1993

Analysis of spontaneous tumor-specific CD4 T-cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with chemotherapy response. Clinical Cancer Research 18(10): 2943-2953, 2012

CD8+ and CD4+ T cell-mediated immunity against novel EphA2-derived epitopes in patients with renal cell carcinoma. FASEB Journal 17(7): C333, April 14, 2003

Differential antibody responses to Plasmodium falciparum-derived B-cell epitopes induced by diepitope multiple antigen peptides (MAP) containing different T-cell epitopes. Vaccine 23(3): 343-352, 2004

Identification of serotype-specific and nonserotype-specific B-cell epitopes of coxsackie B virus using synthetic peptides. Virology 200(2): 381-389, 1994