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1.
Multitargeting involves the application of molecules that are deliberately intended to bind to two or more unrelated cellular targets with high affinity. In epigenetic chemical biology and drug discovery, the rational design of multitargeting agents has evolved to a sophisticated level, and there are now five examples that have reached clinical trials. This review covers recent developments in the field and future prospects. 相似文献
2.
T. Noelle Lombana Jack Bevers III Amy M. Berkley Evangeline Toy Ryan Cook 《MABS-AUSTIN》2019,11(1):75-93
As an immune evasion strategy, MICA and MICB, the major histocompatibility complex class I homologs, are proteolytically cleaved from the surface of cancer cells leading to impairment of CD8 + T cell- and natural killer cell-mediated immune responses. Antibodies that inhibit MICA/B shedding from tumors have therapeutic potential, but the optimal epitopes are unknown. Therefore, we developed a high-resolution, high-throughput glycosylation-engineered epitope mapping (GEM) method, which utilizes site-specific insertion of N-linked glycans onto the antigen surface to mask local regions. We apply GEM to the discovery of epitopes important for shedding inhibition of MICA/B and validate the epitopes at the residue level by alanine scanning and X-ray crystallography (Protein Data Bank accession numbers 6DDM (1D5 Fab-MICA*008), 6DDR (13A9 Fab-MICA*008), 6DDV (6E1 Fab-MICA*008). Furthermore, we show that potent inhibition of MICA shedding can be achieved by antibodies that bind GEM epitopes adjacent to previously reported cleavage sites, and that these anti-MICA/B antibodies can prevent tumor growth in vivo. 相似文献
3.
Paliakkara L. Jaison Vadakkedath M. Kannan Mandagini Geetha Padinjaradath S. Appukuttan 《Journal of biosciences》1993,18(2):187-193
Naturally occurring serum IgG against terminal α-galactoside epitopes (anti-Gal), present exclusively in man, apes and old
world monkeys, was used as probe for these epitopes in human brain. Human brain grey matter soluble glycoproteins enriched
inα galactosyl groups by affinity chromatography on jacalin-sepharose, specifically binds to human anti-Gal in immuno dot
blots. Anti-Gal recognized exclusively the terminal α galactoside epitope in human brain glycoproteins since binding was abolished
by the presence of 1-0-methyl α-D-galactopyranoside as well as by pretreatment of glycoproteins with coffee bean α-galactosidase.
Anti-Gal-peroxidase staining of jacalin-binding human brain glycoproteins in western immuno blots revealed mainly five anti-Gal-binding
polypeptides withM
r
(in kDa) of 94, 108, 180, 210 and 230 respectively. Since the presence of anti-Gal in higher animals accompanies suppression
of the corresponding epitope in most tissues, apparently to maintain immunological balance, possible implications of the above
observation for autoimmunity, tumor metastasis and infection are discussed. 相似文献
4.
5.
《Bioscience, biotechnology, and biochemistry》2013,77(7):1181-1182
The epitopes of the major soybean allergen, Gly m Bd 30K, recognized by mouse monoclonal antibodies H6 and F5 were investigated by using synthetic peptides bound to pins. The epitopes are shown to be localized in peptide 31QGGCGRGWAFSATGAI-EA48 for H6, and in 115 DKVTIDGYETLIMSDEST132 for F5. 相似文献
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8.
Lidia Poplawska-Szczyglowska Jan Walewski Barbara Pienkowska-Grela Grzegorz Rymkiewicz Olga Mioduszewska 《Cancer immunology, immunotherapy : CII》1999,16(1):65-68
A 68-year-old man presented with hemiparesis, lymphocytosis, and cerebral lesions on MRI. Flow cytometry of blood, bone marrow
and cerebrospinal fluid showed B-CLL lymphocytes with bright CD20 expression, slg, and absence of CD23 antigen. Fluorescencein situ hybridisation showed trisomy 12 in 50% of analysed peripheral mononuclear cells. The patient died 6 months after the diagnosis.
Rapidly progressive and fatal course of the disease was consistent with known bad prognostic significance of CD20 bright expression
and trisomy 12. 相似文献
9.
《Cell》2021,184(22):5593-5607.e18
10.
《Cell cycle (Georgetown, Tex.)》2013,12(7):1455-1467
Members of the ErbB receptor family are targets of a growing numbers of small molecules and monoclonal antibodies inhibitors currently under development for the treatment of cancer. Although historical efforts have been directed against ErbB1 (EGFR) and ErbB2 (HER2/neu), emerging evidences have pointed to ErbB3 as a key node in the activation of proliferation/survival pathways from the ErbB receptor family and have fueled enthusiasm toward the clinical development of anti-ErbB3 agents. In this study, we have evaluated the potential therapeutic efficacy of a set of three recently generated anti-human ErbB3 monoclonals, A2, A3 and A4, in human primary melanoma cells. We show that in melanoma cells expressing ErbB1, ErbB3 and ErbB4 but not ErbB2 receptor ligands activate the PI3K/AKT pathway, and this leads to increased cell proliferation and migration. While antibodies A3 and A4 are able to potently inhibit ligand-induced signaling, proliferation and migration, antibody A2 is unable to exert this effect. In attempt to understand the mechanism of action and the basis of this different behavior, we demonstrate, through a series of combined approaches, that antibody efficacy strongly correlates with antibody-induced receptor internalization, degradation and inhibition of receptor recycling to the cell surface. Finally, fine epitope mapping studies through a peptide array show that inhibiting vs. non-inhibiting antibodies have a dramatically different mode of binding to the to the receptor extracellular domain. Our study confirms the key role of ErbB3 and points to exploitation of novel combination therapies for treatment of malignant melanoma. 相似文献