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Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen.
Cancer Res 2000; 60(18):5228-36CR

Abstract

It is accepted that both helper and CTLs play a critical role in immune antitumor responses. Thus, the design of effective immune-based therapies for cancer relies in the identification of relevant tumor-associated antigens (TAAs) capable of eliciting strong helper and cytotoxic T-cell responses against tumor cells. The product of the HER2/neu oncogene is considered as a prototype TAA, because it is found overexpressed in a large variety of malignancies, whereas normal cells only produce low levels of this product. Several cytotoxic T-cell epitopes for HER2/neu have been identified that enable the design of peptide-based therapeutic vaccines for tumors expressing this TAA. Nevertheless, it is expected that inclusion of peptide epitopes capable of eliciting HER2/neu-specific T helper responses into these vaccines may enhance their effectiveness in the clinic. We describe here a strategy to identify helper T-cell epitopes for HER2/neu that focuses on peptides predicted to bind to numerous histocompatibility alleles (promiscuous epitopes), which would encourage their use in therapeutic vaccines for the general cancer patient population. Following this approach, we successfully identified several peptides that elicited T helper (CD4+) proliferative responses to peptides derived from HER2/neu. Most of the T-cell responses appeared to reflect a low affinity for antigen, which could be the result of immune tolerance because HER2/neu is expressed in low levels in normal cells and possibly including lymphocytes and monocytes. Interestingly, one of these peptides, HER2(883), was recognized by T cells in the context of either HLA-DR1, HLA-DR4, HLA-DR52, and HLA-DR53, indicating a high degree of histocompatibility promiscuity. Furthermore, T cells that reacted with peptide HER2(883) could also recognize antigen-presenting cells that process HER2/neu recombinant protein. These results may be relevant for the design of more effective therapeutic vaccines for tumors expressing the HER2/neu oncogene product.

Authors+Show Affiliations

Department of Immunology and Cancer Center, Mayo Clinic and Mayo Graduate School, Rochester, Minnesota 55905, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11016652

Citation

Kobayashi, H, et al. "Defining Promiscuous MHC Class II Helper T-cell Epitopes for the HER2/neu Tumor Antigen." Cancer Research, vol. 60, no. 18, 2000, pp. 5228-36.
Kobayashi H, Wood M, Song Y, et al. Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. Cancer Res. 2000;60(18):5228-36.
Kobayashi, H., Wood, M., Song, Y., Appella, E., & Celis, E. (2000). Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. Cancer Research, 60(18), pp. 5228-36.
Kobayashi H, et al. Defining Promiscuous MHC Class II Helper T-cell Epitopes for the HER2/neu Tumor Antigen. Cancer Res. 2000 Sep 15;60(18):5228-36. PubMed PMID: 11016652.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. AU - Kobayashi,H, AU - Wood,M, AU - Song,Y, AU - Appella,E, AU - Celis,E, PY - 2000/10/4/pubmed PY - 2000/10/21/medline PY - 2000/10/4/entrez SP - 5228 EP - 36 JF - Cancer research JO - Cancer Res. VL - 60 IS - 18 N2 - It is accepted that both helper and CTLs play a critical role in immune antitumor responses. Thus, the design of effective immune-based therapies for cancer relies in the identification of relevant tumor-associated antigens (TAAs) capable of eliciting strong helper and cytotoxic T-cell responses against tumor cells. The product of the HER2/neu oncogene is considered as a prototype TAA, because it is found overexpressed in a large variety of malignancies, whereas normal cells only produce low levels of this product. Several cytotoxic T-cell epitopes for HER2/neu have been identified that enable the design of peptide-based therapeutic vaccines for tumors expressing this TAA. Nevertheless, it is expected that inclusion of peptide epitopes capable of eliciting HER2/neu-specific T helper responses into these vaccines may enhance their effectiveness in the clinic. We describe here a strategy to identify helper T-cell epitopes for HER2/neu that focuses on peptides predicted to bind to numerous histocompatibility alleles (promiscuous epitopes), which would encourage their use in therapeutic vaccines for the general cancer patient population. Following this approach, we successfully identified several peptides that elicited T helper (CD4+) proliferative responses to peptides derived from HER2/neu. Most of the T-cell responses appeared to reflect a low affinity for antigen, which could be the result of immune tolerance because HER2/neu is expressed in low levels in normal cells and possibly including lymphocytes and monocytes. Interestingly, one of these peptides, HER2(883), was recognized by T cells in the context of either HLA-DR1, HLA-DR4, HLA-DR52, and HLA-DR53, indicating a high degree of histocompatibility promiscuity. Furthermore, T cells that reacted with peptide HER2(883) could also recognize antigen-presenting cells that process HER2/neu recombinant protein. These results may be relevant for the design of more effective therapeutic vaccines for tumors expressing the HER2/neu oncogene product. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11016652/Defining_promiscuous_MHC_class_II_helper_T_cell_epitopes_for_the_HER2/neu_tumor_antigen_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11016652 DB - PRIME DP - Unbound Medicine ER -