The differentiation antigen NY-BR-1 is a potential target for antibody-based therapies in breast cancer
- PMID: 17330232
- DOI: 10.1002/ijc.22620
The differentiation antigen NY-BR-1 is a potential target for antibody-based therapies in breast cancer
Abstract
Antibody-based cancer immunotherapy relies on the identification and characterization of target antigens and the development of potent antibodies recognizing the target. Here we report the expression analysis and molecular characterization of the differentiation antigen NY-BR-1, which we previously identified by using the SEREX (serological analysis of recombinant cDNA expression libraries) method. Corroborating methodologies, including mRNA quantitation and immunoblotting show that NY-BR-1 is strongly expressed in >70% of 129 breast tumors. Application of a NY-BR-1 specific antibody demonstrated NY-BR-1 expression in primary and metastastic breast cancers. In contrast, most of the breast cancer cell lines tested, expressed only low NY-BR-1 levels. Importantly, confocal microscopy revealed that ectopically expressed NY-BR-1 localizes to the cytoplasm and the cell membrane. NY-BR-1 localization in breast cancer specimens was also confirmed by immunohistochemistry. Bioinformatic analysis and deletion mutagenesis further show that NY-BR-1 membrane localization is mediated by 2 cis-active membrane targeting domains. Biochemical surface labeling and FACS analysis of live cells further characterize NY-BR-1 as a transmembrane protein, which can be specifically recognized by the anti-NY-BR-1 antibody on the surface of vital cells. The strong expression of NY-BR-1 in breast tumors, its cytoplasmic and membrane localization and accessibility to an ectopically applied antibody now suggest to pursue NY-BR-1 as a potential target for antibody-based therapies in breast cancer patients.
Similar articles
-
Humoral and cellular immune responses against the breast cancer antigen NY-BR-1: definition of two HLA-A2 restricted peptide epitopes.Cancer Immun. 2005 Dec 12;5:11. Cancer Immun. 2005. PMID: 16335914
-
Identification of tumor-restricted antigens NY-BR-1, SCP-1, and a new cancer/testis-like antigen NW-BR-3 by serological screening of a testicular library with breast cancer serum.Cancer Immun. 2002 Jun 28;2:5. Cancer Immun. 2002. PMID: 12747750
-
NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy.Cancer Immunol Immunother. 2007 Nov;56(11):1723-31. doi: 10.1007/s00262-007-0316-1. Epub 2007 Apr 5. Cancer Immunol Immunother. 2007. PMID: 17410359 Free PMC article.
-
Potential target antigens for immunotherapy identified by serological expression cloning (SEREX).Methods Mol Biol. 2007;360:319-26. doi: 10.1385/1-59745-165-7:319. Methods Mol Biol. 2007. PMID: 17172736 Review.
-
NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives.Front Immunol. 2018 May 1;9:947. doi: 10.3389/fimmu.2018.00947. eCollection 2018. Front Immunol. 2018. PMID: 29770138 Free PMC article. Review.
Cited by
-
Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications.BMC Cancer. 2013 Jun 3;13:271. doi: 10.1186/1471-2407-13-271. BMC Cancer. 2013. PMID: 23731661 Free PMC article.
-
Novel genes associated with lymph node metastasis in triple negative breast cancer.Sci Rep. 2015 Nov 5;5:15832. doi: 10.1038/srep15832. Sci Rep. 2015. PMID: 26537449 Free PMC article.
-
In silico SNP analysis of the breast cancer antigen NY-BR-1.BMC Cancer. 2016 Nov 18;16(1):901. doi: 10.1186/s12885-016-2924-7. BMC Cancer. 2016. PMID: 27863482 Free PMC article.
-
Breast cancer vaccines delivered by dendritic cell-targeted lentivectors induce potent antitumor immune responses and protect mice from mammary tumor growth.Vaccine. 2017 Oct 13;35(43):5842-5849. doi: 10.1016/j.vaccine.2017.09.017. Epub 2017 Sep 12. Vaccine. 2017. PMID: 28916248 Free PMC article.
-
Novel chimeric antigen receptors for the effective and safe treatment of NY-BR-1 positive breast cancer.Clin Transl Med. 2024 Jul;14(7):e1776. doi: 10.1002/ctm2.1776. Clin Transl Med. 2024. PMID: 39032146 Free PMC article. No abstract available.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases