-. Plunkett, M. L., M. E. Sanders, P. Selvaraj, M. L. Dustin, T. A. Springer. Would you like email updates of new search results? Would you like email updates of new search results? Emil von Behring suggested in the early 1890s that immunity stemmed from protective substances in blood serum (the clear liquid portion of the blood that separates out upon clotting), which he called antibodies. Macrophage-platelets interaction in diabetic conditions (in cooperation with AG Prof. Bugert), Systems immunology analysis of macrophage responses to titanium and coating materials (EU FP7 IMMODGEL), Anti-inflammatory macrophages for implants and regenerative medicine (EU FP7 IMMODGEL), Detrimental macrophage differentiation in heart failure patient undergoing therapy with left ventricular assist device, Biological functions and role of YKL-39 in cancer progression, Alphavirus-based delivery of chitinase-like-protein gene for anti-tumour programing of macrophages (ERANET-Rus plus). Spleen cells isolated from immunized animals were fused with Ag8-PAI (provided by M. Kramer, Institut für Immunologie, Heidelberg, Germany). B, Suboptimal stimulation by M1 and M2 allows further costimulation by CD58. Heidelberger focused on such immunological cross reactions for the next six decades because they allowed inferences about the chemical structure of polysaccharide antigens, and about how their structure determined their reactions with other antigens and with antibodies. Clinical Chemistry, Laboratory of the Surgical Clinic, Heidelberg University, Germany. Note that all purified–blocking Abs (T111) were equally effective at concentrations of 2 μg/ml. 2023 Apr 21. doi: 10.1038/s41575-023-00771-6. AS/CD tumor regression occurred independently of 5-fluorocytosine treatment and was sufficient to protect 37% of the animals against subsequent challenge with tumorigenic doses of the parental AS cell line. In these assays the BsAb has to be supplemented by the trigger Ab M1(Fab′)2 to achieve activation. 2016 Jul 29;7:12343. -, Diehl, A. M. & Day, C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. Purification of intermediate products (Fab′, Fab′-TNB) as well as the final purification of BsAb was performed by gel filtration on a Superdex 200 column (Pharmacia). Hands-on skills in epigenetic techniques such as ATAC-seq, ChIP-seq, or CUT…. Brennan, M., P. F. Davidson, H. Paulus. 2017 Jan;222(1):101-109, Moganti K, Li F, Schmuttermaier C, Riemann S, Klüter H, Gratchev A, Harmsen MC, Kzhyshkowska J J. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages. : 06221 56-4000 Fax: 06221 56-5990 . Both types of macrophages can have detrimental effects on . The amount of antibodies, which many immunologists (but not all) had long assumed to be proteins, was indicated by the quantity of nitrogen found in the resulting antigen-antibody precipitates, because antibody proteins, like almost all other proteins, contained nitrogen, while polysaccharides did not. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Furthermore, the kinetics of biodistribution of M2xEGF-R have been determined in experimental animals to gain data on the optimal period of time needed for targeting by the BsAb (W. Strittmatter, C. Jaggle, and S. Matzku, manuscript in preparation). Their experiments further revealed the physiochemical heterogeneity of antibodies, which often combine in complex patterns in precipitating antisera (and may not precipitate with antigen when separated from other precipitating antibodies with which they are normally associated). BsAb M2xEGF-R causes limited modulation of the CD2 molecule. Authors and Affiliations. CD2 offers the advantage of being strongly expressed by all T lymphocytes and virtually all NK cells independent of their differentiation and activation stage (2). Clipboard, Search History, and several other advanced features are temporarily unavailable. Inclusion Criteria: newly diagnosed acute lymphoblastic leukemia; age ≥ 1 year (> 365 days) and < 18 years old (up to 17 years old and 365 days) Required fields are marked *. PBMC (○) and purified T cells (•) were incubated with a combination of mAbs M1 and M2 in different concentrations. Titanium and titanium alloys have been successfully used in orthopedics, dentistry, cardiology and otorhinolaryngology. Weiner, G. J., S. A. Kostelny, J. R. Hillstrom, M. S. Cole, B. K. Link, S. L. Wang, J. Yun Tso. Fig. hum.) Gut-liver axis: barriers and functional circuits. Finally, besides their therapeutic application in vivo M1 plus M2xEGF-R Abs could be valuable for ex vivo tumor cell purging. 8600 Rockville Pike Numbers in brackets indicate the percentages of positively stained cells. & Heikenwälder, M. From NASH to HCC: current concepts and future challenges. An official website of the United States government. Samples were then washed again and incubated with goat anti-mouse IgG3-FITC (note that T113 is of the IgG3 isotype whereas all other mAbs employed here are IgG1). Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation. Immunobiology. Subsequently, the samples were washed, a saturating concentration of mAb T11–3 was added to each sample, and they were incubated at 4°C for 30 min. In the second step (“activation phase”) trigger Ab M1(Fab)2 will be delivered which should activate only those lymphocytes that have been targeted by BsAb M2xEGF-R, thus allowing a preferential local activation. eCollection 2023. Gückel, B., C. Berek, M. Lutz, P. Altevogt, V. Schirrmacher, B. Six wells containing target cells in 1% Nonidet P-40 detergent were used for determining maximum release (MR). 16, 411–428 (2019). Nov 3, 2022 1 1 1 The German Cancer Research Center (DKFZ) invites application for vacant PhD, Postdoc and Academic Positions, the largest biomedical institution in Germany in the field of cancer research. F(ab′)2 fragments were purified by chromatography on protein A Sepharose. mAb OKT11 was not included in this assay but had previously been reported to inhibit CD3-driven proliferation of T cells as well (21). Bethesda, MD 20894, Web Policies Epub 2019 Oct 4. The CD2 specific mAb M2 as well as EGF-R mAb 425 were cleaved into F(ab′)2 and converted into Fab′ fragments. Rodeck, U., M. Herlyn, C. Molthoff, et al. We have examined both parental CD2 Abs M1 and M2 and other CD2 mAbs for interference with this kind of activation. Nat. No previous study analyzing the performance of a combination of CD2 × TA BsAb and CD2-trigger-Ab (36, 37, 38) had demonstrated that such a combination of Abs can induce cytotoxicity in resting PBMC. Despite significant advance in our understanding of the fundamental aspects of cancer cell biology and development of novel therapeutic tools, cancer remains to be one of most significant health problem world-wide. Yellow fever control: current epidemiology and vaccination strategies. 9) and for their in vitro function in autologous systems (W. Strittmatter, C. Jäggle, and S. Matzku, unpublished data). However, failure of macrophages to resolve the inflammation and their tendency to stay in a state of "frustrated phagocytosis leads to the chronic inflammation accompanied by microbial contamination and resulting in the implant failure. Lindauer, M., W. Rudy, B. Gückel, M. v. Knebel-Doeberitz, S. C. Meuer, U. Moebius. MeSH government site. government site. 1, 15080 (2015). Hierzu bedient sie sich der Methoden der Mikrobiologie, Inneren Medizin, Epidemiologie und Hygiene. Importantly, the need for trigger Ab M1 for effector cell stimulation allowed to separate targeting from triggering steps in vitro and should thus enable to focus immune responses to sites of target Ag expression in vivo. Tumor infiltrating lymphocytes (TIL) have been prepared as described previously from freshly resected melanoma tissue (12) and have been stimulated via mixed lymphocyte tumor cell culture (MLTC) (13). However, at least one point can me made: there is ample experience from studies on large Ab panels, e.g., CD clusters that have clearly demonstrated that functional Ab activities often relate to molecular features of the Abs themselves (which in spite of extensive investigations on their avidities, isotypes, or molecules/epitopes to which they bind are far from being understood). E-mail address: m66@ix.urz.uni-heidelberg.de, Martin K. Wild, Wolfgang Strittmatter, Siegfried Matzku, Burkhart Schraven, Stefan C. Meuer; Tumor Therapy with Bispecific Antibody: The Targeting and Triggering Steps Can Be Separated Employing a CD2-Based Strategy. He was "convinced that it was necessary for progress in immunology to have some better methods than just titrations and dilution end points . Meuer, S. C., R. E. Hussey, M. Fabbi, D. Fox, O. Acuto, K. A. Fitzgerald, J. C. Hodgdon, J. P. Protentis, S. F. Schlossman, E. L. Reinherz. Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1+ cDC1 as an important driver of liver pathology. Following two washes cells were stained for 15 min at 4°C with steptavidin-FITC conjugate (Becton Dickinson, San Jose, CA), washed again, and analyzed on an EPICS Profile flow cytometer (Coulter Electronics, Hialeah, FL). PMC Hyperglycaemia activates both oxidative stress and inflammatory pathways leading to the progression of diabetes and vascular complications. This phenomenon may be due to inhibition of activation via the TCR/CD3 complex. One concept to circumvent impaired effector-cell/tumor-cell interactions in malignant disease relates to the use of bispecific mAbs (BsAbs)3 that can simultaneously bind tumor cells and effector cells and activate the latter in a diseased organ. In some of the experiments, immunoaffinity purified recombinant human CD58 (17) was added to the cultures. Accessibility In short, the freshly isolated lymphocytes were cocultured with autologous irradiated melanoma bulk culture tumor cells in RPMI 1640 medium supplemented with 20 U/ml IL-2 (Genzyme, Cambridge, MA) and 10% FCS. Specifically, they showed them to be modified serum globulins, a class of proteins that are insoluble in water but are soluble in saline solutions. Biological markers may add to prediction of outcome achieved by the International Prognostic Score in Hodgkin's disease.Ann Oncol 2000; 11: 1405-1411 ; 2 Bien E, Balcerska A. Serum soluble interleukin-2 receptor, beta2-microglobulin, lactate dehydrogenase and erythrocyte sedimentation rate in children with Hodgkin's lymphoma. This site needs JavaScript to work properly. Essential features of macrophages include their functional and phenotype diversity and plasticity that makes them attractive targets for the therapeutic programming. Diabetes is associated with a number of macro- and microvascular complications leading to the failure of organs such as the heart, kidneys and eyes. Alternatively, a CD3 × TA BsAb-mediated reduction of surface expression of the TCR/CD3 complex (modulation) (28) is possible, which would lead to an inability to bind MHC/Ag complexes. Screening of CD2 specific hybridoma supernatants was done by measuring Ab binding to Jurkat T cells in cytometry analyses. 4). Schraven, B., M. Roux, B. Hutmacher, S.C. Meuer. Careers, Michael Heidelberger - Profiles in Science, The Making of an Immunologist: Heidelberger's Years at the Rockefeller Institute, 1912-1927, "If I Have a Few More Years to Work, I'm Going Ahead": An Active Retirement, 1954-1991. Dengler, T. J., J. C. Hoffmann, P. Knolle, M. Albert-Wolf, M. Roux, R. Wallich, S. C. Meuer. Haack, K., Linnebacher, M., Eisold, S. et al. Such phagocytic cells, it was soon suggested, required that bacteria be coated by antibody before they could effectively kill them. 2019 Sep 2;26(6):taz024. Es beschäftigt sich mit der Diagnostik und Erforschung des menschlichen Immunsystems und seiner Bedeutung für eine Vielzahl chronischer, unheilbarer Erkrankungen. A yield of purified BsAb of 20–30% based on the F(ab′)2 starting material was achieved and is demonstrated in Fig. 2016 Jul 22. pii: S0171-2985(16)30325-4. doi: 10.1016/j.imbio.2016.07.006. 2018 Dec 4;169(11):761-765. doi: 10.7326/M18-1529. 2015;21(9):1172-9. By measuring the weight of complement and evaluating the role of calcium and magnesium ions in complement fixation reactions (the consumption of complement upon reaction with immune complexes containing complement-fixing antibodies, and the basis of complement fixation tests widely used to detect antigens or antibodies), Heidelberger and his students Manfred Mayer, Abraham George Osler, and Otto Bier gave the first indications that complement was a functionally related system of several different serum proteins. The novel CD2 mAbs were tested for noninterference with the CD2-CD58 interaction. Diversity and plasticity of macrophages. Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious adverse events: systematic review. TGF-β1, but not bone morphogenetic proteins, activates Smad1/5 pathway in primary human macrophages and induces expression of proatherogenic genes. Moreover, unlike many Ags that are more specific for malignant cells, the EGF-R does not bear the disadvantage of a strong heterogeneity of expression within a given tumor (31). Conversely, Heidelberger and Kendall added antibody-containing antiserum to a solution of pneumococcal antigens in order to detect polysaccharide. Duration of post-vaccination humoral immunity against yellow fever in children. (*equal last authorship). Zhang JJ, Shen Y, Chen XY, Jiang ML, Yuan FH, Xie SL, Zhang J, Xu F. Front Endocrinol (Lausanne). Moreover, exposure of T cells to CD3 mAb alone can induce anergy (29). The rationale behind this was that bispecific Abs used in, e.g., cancer treatment should not block important T cell functions involving the CD2-CD58 interaction, such as cell-cell adhesion, recirculation of T-lymphocytes as well as costimulation in the activation of T cells through CD2 (17, 19, 24). Nat. PMID: 16688674 DOI: 10.1055/s-2006-933414 Abstract Homozygous sickle cell (HbSS) disease is paradigmatic for the complex influence of genetic modifiers of a monogenic disease. MLTC derived bulk culture TILs have been used to perform cytotoxicity assays. In children vaccinated before age 2 years, the seroprotection rate was 52% within 5 years after primary vaccination. 2011 Nov;166(2):281-90. doi: 10.1111/j.1365-2249.2011.04471.x. Thus, second signals may not be sufficiently available in the case of tumors that would limit the application of CD3 × TA BsAbs. Between the 1920s and the 1940s, Michael Heidelberger began to resolve several of these mysteries by placing immunology on the precise footing of modern biochemistry, and by introducing mathematical and statistical methods to the field. Heidelberger and his collaborators later expanded these methods to protein antigens. Epub 2023 Feb 14. J Travel Med 2019; 26:taz040. government site. FOIA Furthermore, the inserted diagram in Fig. Long-Term Protection After Fractional-Dose Yellow Fever Vaccination: Follow-up Study of a Randomized, Controlled, Noninferiority Trial. ISSN 0929-1903 (print), Gene expression imaging by enzymatic catalysis of a fluorescent probe via membrane-anchored β-glucuronidase, A membrane antibody receptor for noninvasive imaging of gene expression, Antitumor immune responses mediated by adenoviral GDEPT using nitroreductase/CB1954 is enhanced by high-level coexpression of heat shock protein 70, Combined suicide gene therapy for pancreatic peritoneal carcinomatosis using BGTC liposomes. These are the top universities in Germany for immunology, based on their reputation and research in the field. of the Faculty of Medicine, Heidelberg University, Germany, Member of the Research Board of the Faculty of Medicine, Heidelberg University, Germany, Member of the PhD committee (Dr. sc. 1 Universität Heidelberg/MPI für medizinische Forschu ng, Institut für Immunologie, Heidelberg Introduction: Fibronectin is an extracellular matrix protein that is expressed in almost all types . Deusch, K., U. Moebius, K.-H. Meyer zum Büschenfelde, S. C. Meuer. Rai RP, Liu Y, Iyer SS, Liu S, Gupta B, Desai C, Kumar P, Smith T, Singhi AD, Nusrat A, Parkos CA, Monga SP, Czaja MJ, Anania FA, Raeman R. J Hepatol. , and that the main problems of immunology would never be solved unless you could apply analytical microchemistry and get some real data in absolute units." Palmer not only created a congenial academic atmosphere in which Heidelberger thrived, he approached the financier Edward Harkness for money to set up the $500,000 Harkness Research Fund, which paid Heidelberger's salary during his 27 years at Columbia and freed him from the need to apply for research grants. Binding of particular Abs to triggering receptors can result in their total loss from the cell surface through modulation (32, 33, 34). Keywords: Perhaps more importantly, when compared with the widely used targeting to the CD3 complex, the M1- and M2-based targeting of the CD2 molecule may have a critical advantage: previous in vitro studies have shown that binding of CD3 × TA BsAbs to CTL can lead to the inability of these cells to carry out a TCR-specific target cell lysis (27). After fifteen years at the Rockefeller Institute for Medical Research and one year at Mount Sinai Hospital, Heidelberger was offered a position--the first of its kind in the United States--as consulting research chemist to the Department of Medicine of the College of Physicians and Surgeons at Columbia University. Subsequently, 5 × 103 51Cr-labeled A 431 cells were added. For tumor therapy with unprimed effector cells, we developed a novel combination of a CD2 × tumor Ag bispecific targeting Ab and an anti-CD2 triggering Ab. The introduction of more accurate methods of assessing . Its high over-expression on certain tumors should allow to find a range of Ab concentrations that cause preferential damage to malignant cells. Buldakov M, Zavyalova M, Krakhmal N, Telegina N, Vtorushin S, Mitrofanova I, Riabov V, Yin S, Song B, Cherdyntseva N, Kzhyshkowska J. CD68+, but not stabilin-1+ tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer. Heidelberger and his first graduate student and long-time Columbia University colleague, Elvin A. Kabat (1914-2000), subsequently extended this quantitative theory to agglutination, the clumping together of antigen-bearing cells, microorganisms, or particles in suspension by the introduction of specific antibodies (agglutinins). 2 B). ISSN 1476-5500 (online) We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. All cultures had a final volume of 2 ml. Human T cells (2 × 105) were incubated for 30 min with CD2 mAbs (T112 and T113, 1:500-dilution of ascites; all other mAbs, purified Abs at final concentrations of 20 μg/ml. PubMed Google Scholar. In competitive binding ELISAs, the mAbs M1 and M2 cross-blocked with the established anti-CD2 mAb T113 (3) in binding to recombinant CD2 (Fig. Performance of M1 and M2 in CD2- and CD3-driven proliferation of PBMC and T cells. Nonalcoholic fatty liver disease. hum.) Since antibodies contained in antisera can impart a level of immunity when injected into the bloodstream, Heidelberger was able to provide much more effective antiserum for use in immunizations by measuring the quantity of antibody in antiserum and by increasing it accordingly. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Law, A. J. McKnight, M. G Tomlinson, P. A. van der Merwe. Abs M1 (=AICD2.M1, IgG1), M2 (=AICD2.M2, IgG1), and AICD2.5 (IgG1) were produced in our laboratory. Specific lysis of A 431 cells was determined in a 4-h assay. Integrative network-based analysis on multiple Gene Expression Omnibus datasets identifies novel immune molecular markers implicated in non-alcoholic steatohepatitis. Modulation could also be expected in a “targeting” situation in which effector and target cells bind to each other via BsAbs and oligomerize CD2. Europe PMC is an archive of life sciences journal literature. WHO position paper – June 2013. 15 German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. Rev. Ab-coated lymphocytes or BsAb M2xEGF-R should then be targeted to tumor sites. Bispecific and monospecific Abs were added simultaneously or in two steps before supernatants were collected after a total culturing time of 18 h. For the design of CD2 × EGF-R-specific BsAbs we produced anti-CD2 mAbs with a combination of favorable characteristics. Read the methodology ». Values are means of three independent experiments ± SD.
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