Journal ArticleDOI
Anti-MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide
Mark A. Reddish,G D MacLean,R. Rao Koganty,June Kan-Mitchell,Vicky Jones,Malcolm S. Mitchell,B. Michael Longenecker +6 more
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TLDR
The generation of M UC1‐specific CTLs required only a 6‐day in vitro stimulation of patients' T‐cells with synthetic MUC1‐peptide‐pulsed autologous APCs and the assay for CTL activity was a 4 hr 51Cr release from labeled adenocarcinoma target cells.Abstract:
Sixteen metastatic breast cancer patients were immunized with a low dose (5 micrograms) of a 16 amino acid MUC1 peptide (GVTSAPDTRPAPGSTA) conjugated to KLH (BP16-KLH) plus DETOX adjuvant and evaluated for antibody titers against MUC1 peptide and KLH and for cytotoxic lymphocyte (CTL) activity using class 1 HLA-matched MUC1-positive tumor targets. All patients generated strong anti-KLH IgG responses. Only 3 patients developed an anti-MUC1 IgG response, which was weak in magnitude. As it is controversial whether human cancer patients generate class-1-restricted CTL against MUC1, we examined anti-MUC1 CTL activity of PBLs following 4 immunizations with BP16-KLH. The generation of MUC1-specific CTLs required only a 6-day in vitro stimulation of patients' T-cells with synthetic MUC1-peptide-pulsed autologous APCs. The assay for CTL activity was a 4 hour 51Cr release from labeled adenocarcinoma target cells. Eleven of the 16 immunized patients were tested for CTL activity using class-1-matched adenocarcinoma target cell lines. Evidence for class-1-restricted killing of MUC1-expressing tumor cell lines was obtained in 7 of these 11 patients.read more
Citations
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Mucins in cancer: Protection and control of the cell surface
TL;DR: Mucins — large extracellular proteins that are heavily glycosylated with complex oligosaccharides — establish a selective molecular barrier at the epithelial surface and engage in morphogenetic signal transduction.
Journal ArticleDOI
MUC1, the renaissance molecule.
TL;DR: Recent discoveries that suggest that MUC1 may be a multifunctional protein, located on the surfaces of cells as a sensor of the environment, poised to signal to the interior when things go awry are highlighted.
Journal ArticleDOI
MUC1 and cancer
TL;DR: The MUC1 membrane mucin was first identified as the molecule recognised by mouse monoclonal antibodies directed to epithelial cells, and the cancers which develop from them, and its role in the immune response and in other interactions with the effector cells of the immune system is of particular interest.
Journal ArticleDOI
Identification of HLA-A2–Restricted T-Cell Epitopes Derived From the MUC1 Tumor Antigen for Broadly Applicable Vaccine Therapies
Peter Brossart,Kathrin S. Heinrich,Gernot Stuhler,Lars Behnke,Volker L. Reichardt,Stefan Stevanovic,Alexandra Muhm,Hans-Georg Rammensee,Lothar Kanz,Wolfram Brugger +9 more
TL;DR: Two novel peptides with a high binding probability to the HLA-A2 molecule are identified, suggesting that the MUC1-directed immune responses are not limited to the extracellular tandem repeat domain, and could provide a broadly applicable approach for the development of dendritic cell-based vaccination therapies.
Journal Article
Cellular and Molecular Pharmacology of Antiestrogen Action and Resistance
TL;DR: Antiestrogen therapy remains one of the most widely used and effective treatments for the management of endocrine responsive breast cancers, but the mechanisms driving resistance in tumors that express estrogen and/or progesterone receptors are unclear.
References
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Induction of th1 and th2 cd4+ t cell responses : the alternative approaches
TL;DR: The effects on Th priming of (a) using altered peptide ligands as antigens, (b) varying the dose of antigen, and (c) altering costimulatory signals are discussed.
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Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes.
Yutaka Kawakami,Siona Eliyahu,Kazuyasu Sakaguchi,Paul F. Robbins,Licia Rivoltini,John R. Yannelli,Ettore Appella,Steven A. Rosenberg +7 more
TL;DR: One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis and appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies.
Journal ArticleDOI
A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats.
TL;DR: It is shown here that all three antibodies react with a synthetic peptide with an amino acid sequence corresponding to that predicted by the tandem repeat, allowing a directed approach to the development of tumor-specific antibodies using synthetic peptides as immunogens.
Journal Article
Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression.
Yutaka Kawakami,Siona Eliyahu,C. Jennings,Kazuyasu Sakaguchi,Xiaoqiang Kang,Scott Southwood,Paul F. Robbins,Alessandro Sette,Ettore Appella,Steven A. Rosenberg +9 more
TL;DR: Four of ten HLA-A2-restricted melanoma specific CTL that were derived from tumor-infiltrating lymphocytes (TIL) and administered to patients recognized the gp100 melanoma Ag and nine of ten recognized the MART-1 Ag.
Journal ArticleDOI
Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine
TL;DR: This study demonstrates for the first time the ability to generate a human cytolytic T- cell response to specific epitopes of CEA in the context of major histocompatibility complex for T-cell-mediated lysis.