Potent antitumor activity of a tumor-specific soluble TCR/IL-2 fusion protein.

We previously have generated a single-chain T cell receptor-cytokine fusion protein (264scTCR/IL-2) comprising interleukin-2 genetically linked to a soluble HLA-A2.1-restricted TCR recognizing a peptide of human p53 protein. In this report, we show that 264scTCR/IL-2 inhibits the growth of primary tumors derived from the A375 (p53+/HLA-A2.

Visualization of p53(264-272)/HLA-A*0201 complexes naturally presented on tumor cell surface by a multimeric soluble single-chain T cell receptor.

Intracellular Ags are processed into small peptides that are presented on cell surfaces in the context of HLA class I molecules. These peptides are recognized by TCRs displayed by CD8+ T lymphocytes (T cells). To date, direct identification and quantitation of these peptides has relied primarily on mass spectrometry analysis, which is expensive and requires large quantities of diseased tissues to obtain useful results.

In vitro and in vivo characterization of a novel antibody-like single-chain TCR human IgG1 fusion protein.

We have constructed a protein composed of a soluble single-chain TCR genetically linked to the constant domain of an IgG1 H chain. The Ag recognition portion of the protein binds to an unmutated peptide derived from human p53 (aa 264-272) presented in the context of HLA-A2.1, whereas the IgG1 H chain provides effector functions.

Expression, location, and interactions of ErbB2 and its intramembrane ligand Muc4 (sialomucin complex) in rat mammary gland during pregnancy.

Muc4 (also called Sialomucin complex) is a heterodimeric glycoprotein complex consisting of a peripheral O-glycosylated subunit ASGP-1 (ascites sialoglycoprotein-1) tightly but non-covalently bound to an N-glycosylated transmembrane subunit ASGP-2. Muc4/SMC can act as an intramembrane ligand for ErbB2 via an EGF-like domain present in the transmembrane subunit. The complex is developmentally regulated in normal rat mammary gland and overexpressed in a number of mammary tumors.

A soluble single-chain T-cell receptor IL-2 fusion protein retains MHC-restricted peptide specificity and IL-2 bioactivity.

Antibody-based targeted immunotherapy has shown promise as an approach to treat cancer. However, many known tumor-associated antigens are not expressed as integral membrane proteins and cannot be utilized as targets for antibody-based therapeutics. In order to expand the limited target range of antibodies, we have constructed a soluble single-chain T-cell receptor (TCR) fusion protein designated 264scTCR/IL-2.

PEA3 transactivates the Muc4/sialomucin complex promoter in mammary epithelial and tumor cells.

Sialomucin complex (SMC, rat Muc4) is a heterodimeric glycoprotein composed of two subunits, the mucin component ascites sialoglycoprotein ASGP-1 and the transmembrane subunit ASGP-2, which is aberrantly expressed on the surfaces of a variety of tumor cells. Up-regulation of the Muc4/SMC gene in the 13762 sublines of the rat mammary adenocarcinoma correlates with the overexpression of transcription factor PEA3 and the receptor tyrosine kinase ErbB2. Here we report that PEA3 is capable of transactivating the Muc4/SMC promoter in a dose-dependent manner via direct attachment to a PEA3 binding site.

SMAD2 and SMAD7 involvement in the post-translational regulation of Muc4 via the transforming growth factor-beta and interferon-gamma pathways in rat mammary epithelial cells.

Muc4/sialomucin complex (SMC) is a heterodimeric glycoprotein complex derived from a single gene that is post-translationally processed into mucin (ASGP-1) and transmembrane (ASGP-2) subunits. Muc4/SMC is tightly regulated in the rat mammary gland, low in the virgin, increased during pregnancy and lactation, and overexpressed in some aggressive mammary tumors. Investigations of primary rat mammary epithelial cells (MEC) have shown that Muc4/SMC expression is post-translationally regulated through inhibition of Muc4/SMC precursor processing by transforming growth factor-beta (TGF-beta).

Rat Muc4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance.

Muc4 (also called sialomucin complex), the rat homolog of human MUC4, is a heterodimeric glycoprotein complex that consists of a peripheral O-glycosylated mucin subunit, ASGP-1, tightly but noncovalently linked to a N-glycosylated transmembrane subunit, ASGP-2. The complex is expressed in a number of normal, vulnerable epithelial tissues, including mammary gland, uterus, colon, cornea and trachea. Muc4/SMC is also overexpressed or aberrantly expressed on a number of human tumors including breast tumors.

Muc4/sialomucin complex, the intramembrane ErbB2 ligand, in cancer and epithelia: to protect and to survive.

The membrane mucin Muc4, also called sialomucin complex (SMC), is a heterodimeric complex of two subunits, ASGP-1 and ASGP-2, derived from a single gene. It is produced by multiple epithelia in both membrane and soluble forms and serves as a protective agent for the epithelia. The membrane form of Muc4 acts as a steric barrier to the apical cell surface of epithelial or tumor cells.

Sialomucin complex in tumors and tissues.

Sialomucin complex (SMC) is a high Mr glycoprotein heterodimer, originally discovered on the cell surfaces of ascites sublines of the highly metastatic 13762 rat mammary adenocarcinoma, and composed of mucin (ASGP-1) and transmembrane (ASGP-2) subunits. SMC is encoded by a single gene and synthesized as a large precursor protein which is cleaved into its subunits early in its transit to the cell surface. SMC exhibits behavior typical of both membrane and secreted mucins.