Abstract
We describe a recombinant method for the construction and production of a novel IgG-like BsAb molecule, using the variable domains of two fully human antibodies as the building blocks....
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PMID: 19252849
PDF is available here.
Author(s) unavailable
Abstract
The only treatment for malignant ascites in patients with refractory cancer is paracentesis, a procedure to relieve symptoms. Catumaxomab, a monoclonal antibody, is now authorised in the European Union for intraperitoneal administration to patients with epithelial cancers that overexpress epithelial...
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PMID: 21180374
PDF is available here.
Abstract
Peritoneal carcinomatosis remains an unsolved medical problem in modern oncologic treatment. Excruciating symptoms such as malignant ascites, ileus, nausea, vomiting, dyspnoea and pain deteriorate the quality of life for affected patients. There is still no effective standard treatment for peritonea...
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PMID: 20919824
PDF is available here.
Abstract
A novel approach for the selective silencing of targeted autoreactive B lymphocytes is reviewed that mimics the physiological mechanisms for suppressing B cell activity. It is based on the use of bi- or tri-specific chimeric antibodies that cross-link BCRs with a pre-selected antigen...
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PMID: 20601201
PDF is available here.
Maria-Concetta Veri,
Stephen Burke,
Ling Huang,
Hua Li,
Sergey Gorlatov,
Nadine Tuaillon,
G Jonah Rainey,
Valentina Ciccarone,
Tengfei Zhang,
Kay Shah,
Linda Jin,
Lida Ning,
Tamara Minor,
Paul A Moore,
Scott Koenig,
Syd Johnson and
Ezio Bonvini
Abstract
To exploit the physiologic Fcgamma receptor IIb (CD32B) inhibitory coupling mechanism to control B cell activation by constructing a novel bispecific diabody scaffold, termed a dual-affinity retargeting (DART) molecule, for therapeutic applications.
DART molecules wer...
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PMID: 20506263
PDF is available here.
Kannan Gunasekaran,
Martin Pentony,
Min Shen,
Logan Garrett,
Carla Forte,
Anne Woodward,
Soo Bin Ng,
Teresa Born,
Marc Retter,
Kathy Manchulenko,
Heather Sweet,
Ian N Foltz,
Michael Wittekind and
Wei Yan
Abstract
We have modified the CH3 domain interface of the antibody Fc region with selected mutations so that the engineered Fc proteins preferentially form heterodimers. These novel mutations create altered charge polarity across the Fc dimer interface such that coexpression of electrostatically matched Fc c...
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PMID: 20400508
PDF is available here.
Rafke R Schoffelen,
Robert M RM Sharkey,
David M DM Goldenberg,
Gerben G Franssen,
William J WJ McBride,
Edmund A EA Rossi,
Chien-Hsing CH Chang,
Peter P Laverman,
Jonathan A JA Disselhorst,
Annemarie A Eek,
Winette T A WT van der Graaf,
Wim J G WJ Oyen and
Otto C OC Boerman
Abstract
(18)F-Fluorodeoxyglucose ((18)F-FDG) is the most common molecular imaging agent in oncology, with a high sensitivity and specificity for detecting several cancers. Antibodies could enhance specificity; therefore, procedures were developed for radiolabeling a small ( approximately 1451 Da) hapten pep...
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PMID: 20354120
PDF is available here.
Abstract
The concept of using bispecific antibodies to retarget immune effector cells for cancer therapy was conceived more than 20 years ago. However, initial clinical studies were rather disappointing mainly due to low efficacy, severe adverse effects and immunogenicity of the bispecific antibodies. A deep...
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PMID: 20199124
PDF is available here.
Abstract
Sprague-Dawley rats (group I) were injected with surrogate antigen-coated beads (SA beads) in the right hind leg or unmodified beads in the contralateral hind leg. In group II, femoral artery de-endothelialization was induced in the left hind leg and sham operation was performed in the contralateral...
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PMID: 20087237
PDF is available here.
Robert R Mabry,
Katherine E KE Lewis,
Margaret M Moore,
Patricia A PA McKernan,
Thomas R TR Bukowski,
Kristen K Bontadelli,
Ty T Brender,
Shannon S Okada,
Karen K Lum,
James J West,
Joseph L JL Kuijper,
Dan D Ardourel,
Secil S Franke,
Luann L Lockwood,
Tuyen T Vu,
Amanda A Frank,
Mark W MW Appleby,
Anitra A Wolf,
Brian B Reardon,
Nels B NB Hamacher,
Brenda B Stevens,
Patsy P Lewis,
Kenneth B KB Lewis,
Debra G DG Gilbertson,
Megan M Lantry,
Susan H SH Julien,
Craig C Ostrander,
Chung C Chan,
Kelly K Byrnes-Blake,
Jennifer J Brody,
Scott S Presnell,
Brent B Meengs,
Steven D SD Levin and
Mark M Snavely
Abstract
We incorporate selection of stable, potent single-chain variable fragments (scFvs) early in the engineering process to assemble bsAbs for therapeutic applications targeting the cytokines IL-17A/A and IL-23. Stable scFvs directed against human cytokines IL-23p19 and IL-17A/A were isolated from a huma...
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PMID: 20022918
PDF is available here.
Abstract
Imaging of colorectal cancer using a 2-step, pretargeting system produced the best imaging results 24 hours after peptide administration using a 4-day interval between injection of the bsAb and the peptide.
(c) 2010 American Cancer Society....
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PMID: 20127959
PDF is available here.
Abstract
We developed cells which constantly express a humanized antibody, and we performed anticancer humanized antibody therapy involving cell transplantation. Genes with the same amino acid sequence as that of the variable region of trastuzumab (Herceptin) as the humanized anti-HER2 monoclonal antibody we...
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PMID: 20043129
PDF is available here.
Abstract
Antibodies are highly versatile proteins with the ability to be used to target diverse compounds, such as radionuclides for imaging and therapy, or drugs and toxins for therapy, but also can be used unconjugated to elicit therapeutically beneficial responses, usually with minimal toxicity. This upda...
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PMID: 20187791
PDF is available here.
Abstract
Myriad bi-specific proteins have been developed that recognize two different clinical targets, with the goal of achieving enhanced therapeutic effects as compared with proteins that interact with only one target. These engineered proteins are starting to enter clinical testing for a...
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PMID: 20371477
PDF is available here.
Abstract
We studied over the last years the activation of human T cells for tumor attack. To this end, we combined the personalized therapeutic tumor vaccine ATV-NDV--which is obtained by isolation, short in vitro culture, irradiation, and infection of patient's tumor cells by Newcastle Disease Virus (NDV)--...
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PMID: 21403859
PDF is available here.
Abstract
We designed, expressed, purified, and tested the neutralization potencies of CD4-CD4i antibody reagents with different architectures, antibody combining sites, and linkers. We found that fusing CD4 to the heavy chain of the CD4i antibody E51 yields a bivalent reagent including an antibody Fc region...
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PMID: 19864392
PDF is available here.
Abstract
Monoclonal antibodies have emerged as a very successful class of therapeutic agents. In their native format, monoclonal antibodies are monospecific in that they recognize only one epitope, but their Fc domain also binds to FcfR-expressing cells. Attempts to improve the cytotoxicity of antibodies, pa...
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PMID: 20035697
PDF is available here.
Abstract
Targeting cell surface antigens or receptors with lytic monoclonal antibodies and specific ligand-directed fusion proteins in order to eliminate cancer cells has been in development for at least forty years. More recently, leukocyte populations known to drive a host of allergic, auto...
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PMID: 19607646
PDF is available here.
Abstract
With 23 approvals in the US and other countries and four approvals outside US, antibodies are now widely recognized as therapeutic molecules. The therapeutic and commercial successes met by rituximab, trastuzumab, cetuximab and other mAbs have inspired antibody engineers to improve the efficacy of t...
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PMID: 20073127
PDF is available here.
Abstract
Bispecific antibodies are capable of interacting with two different antigens and when selected properly, can redirect cytotoxic effector cells to tumor cells for effective killing. These antibodies are therefore of great interest in the research and development of cancer treatment. Over the last two...
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PMID: 20016854
PDF is available here.
Abstract
We report the construction, purification, and characterization of Affitoxin-a novel class of HER2-specific cytotoxic molecules combining HER2-specific Affibody molecule as a targeting moiety and PE38KDEL, which is a truncated version of Pseudomonas exotoxin A, as a cell killing agent. It is highly s...
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PMID: 19752752
PDF is available here.
Abstract
We evaluated the anti-tumour efficiency of bispecific EpCAMxCD3 antibody linking tumour cells and T lymphocytes. In NOD SCID mice, EpCAMxCD3 had a long serum half-life (t(1/2) approximately 7 days). EpCAMxCD3 significantly retarded growth of BxPC-3 pancreatic carcinoma xenografts. For mimicking a pa...
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PMID: 20196789
PDF is available here.
Abstract
The trifunctional bispecific monoclonal antibody catumaxomab has two binding specificities directed at epithelial cell adhesion molecule (EpCAM) and the T-cell antigen CD3. With its Fc-fragment, catumaxomab additionally binds accessory cells such as dendritic cells, macrophages and n...
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PMID: 19927225
PDF is available here.
Abstract
HER2 (human epidermal-growth-factor receptor-2; ErbB2) and EGFR (epidermal-growth-factor receptor) are overexpressed in various forms of cancer, and the co-expression of both HER2 and EGFR has been reported in a number of studies. The simultaneous targeting of HER2 and EGFR has been discussed as a s...
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PMID: 19492986
PDF is available here.
Abstract
The trifunctional antibody catumaxomab with bispecificity for the epithelial cell adhesion molecule EpCAM and the T-cell antigen CD3, is a new therapeutic strategy for ovarian cancer patients with symptomatic malignant ascites. Whether or not intraperitoneal (i.p.) catumaxomab-therapy has influence...
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PMID: 19443405
PDF is available here.
Ralf Lutterbuese,
Tobias Raum,
Roman Kischel,
Petra Lutterbuese,
Bernd Schlereth,
Evelyne Schaller,
Susanne Mangold,
Doris Rau,
Petra Meier,
Peter A Kiener,
Kathy Mulgrew,
Michael D Oberst,
Scott A Hammond,
Patrick A Baeuerle and
Peter Kufer
Abstract
We constructed a series of bispecific single-chain antibodies (bscAb) combining various single-chain variable fragments recognizing human CEA with a deimmunized single-chain variable fragments recognizing human CD3. CEA/CD3-bscAbs redirected human T cells to lyse CEA-expressing tumor cells in vitro...
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PMID: 19342971
PDF is available here.
Abstract
We describe an antibody with an antigen binding site that binds two distinct proteins with high affinity. We isolated a variant of Herceptin, a therapeutic monoclonal antibody that binds the human epidermal growth factor receptor 2 (HER2), on the basis of its ability to simultaneously interact with...
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PMID: 19299620
PDF is available here.
Abstract
In recent decades, mAbs have emerged as therapeutics. Nine mAbs have been approved for cancer therapy. However, the efficiency of mAbs is far from optimal, and antibody engineering is actively used to improve the molecules. Because of their ability to simultaneously bind two different antigens, bisp...
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PMID: 19333873
PDF is available here.
Abstract
Bispecific antibodies, in contrast to conventional monoclonal antibodies, can bind simultaneously two different antigens. Taking advantage of this virtue, they are mostly designed for immune effector cell redirection to tumors and for radionuclide pretargeting to tumors. Bispecific a...
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PMID: 20635943
PDF is available here.
Abstract
We have previously demonstrated preclinical in vivo targeting of prostate stem cell antigen (PSCA) using a humanized anti-PSCA 2B3 monoclonal antibody (mAb). However, humanization resulted in 5-fold loss of apparent affinity relative to the parental mAb (1 nM). In this study, diabodies (scFv dimers...
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PMID: 18957406
PDF is available here.
Abstract
Bispecific T-cell-engager (BiTE) antibodies are designed to transiently engage cytotoxic T-cells for lysis of selected target cells. Although this therapeutic concept had been proposed more than two decades ago, BiTE, and also trispecific, antibodies did not achieve clinical proof-of-concept until t...
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PMID: 19169956
PDF is available here.
Martin Sebastian,
Philipp Kiewe,
Wolfgang Schuette,
Daniel Brust,
Christian Peschel,
Folker Schneller,
Karl-Heinz Rühle,
Georg Nilius,
Ralf Ewert,
Sven Lodziewski,
Bernward Passlick,
Wulf Sienel,
Rainer Wiewrodt,
Michael Jäger,
Horst Lindhofer,
Hilke Friccius-Quecke and
Alexander Schmittel
Abstract
We performed this phase 1/2 trial in patients with malignant pleural effusion (MPE). We investigated a series of 3 escalating doses of 5 to 200 microg catumaxomab administered intrapleurally to patients with MPE containing epithelial cell adhesion molecule -positive cells. Primary objectives were de...
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PMID: 19238019
PDF is available here.
Abstract
We have approached this problem by inhibiting their anti-CD3 activity until it is required. Folated anti-human CD3 antibody bispecific conjugates were therefore synthesised in which the folate portion of the conjugates remained free to bind to folate receptor (FR) expressing cancer cells, whilst the...
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PMID: 20068406
PDF is available here.
Abstract
The symposium on Antibodies as Drugs, organized by Keystone Symposia and chaired by J. Marks, (University of California Los Angeles, USA), E.S. Ward (University of Texas Southwestern Medical Center, USA) and L. Weiner (Georgetown University Medical Center, USA), was held in Whistler, British Columbi...
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PMID: 20068403
PDF is available here.
Abstract
Conventionally, antibody phage display has been used to isolate recombinant antibodies that are monovalent in their interaction with target antigens. These antibodies can be reengineered for expression in mammalian cell culture as full-length, monospecific immunoglobulins. An emerging branch of rese...
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PMID: 19554296
PDF is available here.
Abstract
We have described a bispecific PSMA x CD3 diabody with one binding site for the T-cell antigen receptor (TCR-CD3) and another for the Prostate Specific Membrane Antigen (PSMA). It effectively eliminates human prostate cancer cells by redirecting T-lymphocytes in vitro and in vivo. Here, we show that...
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PMID: 19483653
PDF is available here.
Martin Sebastian,
Philipp Kiewe,
Wolfgang Schuette,
Daniel Brust,
Christian Peschel,
Folker Schneller,
Karl-Heinz Rühle,
Georg Nilius,
Ralf Ewert,
Sven Lodziewski,
Bernward Passlick,
Wulf Sienel,
Rainer Wiewrodt,
Michael Jäger,
Horst Lindhofer,
Hilke Friccius-Quecke and
Alexander Schmittel
Abstract
We performed this phase 1/2 trial in patients with malignant pleural effusion (MPE). We investigated a series of 3 escalating doses of 5 to 200 microg catumaxomab administered intrapleurally to patients with MPE containing epithelial cell adhesion molecule -positive cells. Primary objectives were de...
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PMID: 19238019
PDF is available here.
Jennifer S Michaelson,
Stephen J Demarest,
Brian Miller,
Aldo Amatucci,
William B Snyder,
Xiufeng Wu,
Flora Huang,
Samantha Phan,
Sharon Gao,
Adam Doern,
Graham K Farrington,
Alexey Lugovskoy,
Ingrid Joseph,
Veronique Bailly,
Xin Wang,
Ellen Garber,
Jeff Browning and
Scott M Glaser
Abstract
We describe a protein-engineering approach for producing stable, scalable tetravalent IgG-like BsAbs. The stability-engineered IgG-like BsAb was envisioned to target and crosslink two TNF family member receptors, TRAIL-R2 (TNF-Related Apoptosis Inducing Ligand Receptor-2) and LTbetaR (Lymphotoxin-be...
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PMID: 20061822
PDF is available here.
Abstract
We hypothesised that co-targeting the preferred ErbB2/ErbB3 heterodimer with a bispecific single-chain Fv (bs-scFv) antibody would promote increased targeting selectivity over antibodies specific for a single tumour-associated antigen (TAA). In addition, we hypothesised that targeting this important...
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PMID: 18841159
PDF is available here.
Abstract
We previously showed that a transgenic BCR clonotype that is 'dual reactive' for the hapten arsonate (Ars) and nuclear auto-antigens is stimulated to enter the GC response via Ars immunization. However, the participation of this clonotype in this response wanes with time and it gives rise to few mem...
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PMID: 18689725
PDF is available here.
Abstract
We report the utility of in vitro refolding in the preparation of monomorphous hEx3 bispecific diabodies with epidermal growth factor receptor and CD3 retargeting from insoluble aggregates in Escherichia coli. Appropriate interaction between cognate variable heavy and light chains led to the formati...
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PMID: 18621782
PDF is available here.
Abstract
We designed effective recombinant bispecific antibody (BsAb) formats based on hEx3, a humanized bispecific diabody with epidermal growth factor receptor and CD3 retargeting. The bispecific and bivalent IgG-like antibodies engineered from hEx3 (or its single-chain form, hEx3-scDb) and the human Fc re...
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PMID: 18779744
PDF is available here.
Abstract
Antibodies are highly soluble, multidomain proteins that are well suited for biopharmaceutical development; however, engineering antibodies to perform novel activities or to have enhanced clinical utility can have a detrimental effect on their biophysical properties. Various innovative designs, such...
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PMID: 18729019
PDF is available here.
Abstract
BACKGROUND: Gastric cancer is a condition with a high medical need. Even after R0 resection the rate of peritoneal and other distant site recurrences is high. Novel therapeutic approaches include trifunctional antibodies (trAb) that recruit and activate different types of immune effector cells at th...
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PMID: 18694358
PDF is available here.
Abstract
High-precision tumor targeting with conventional therapeutics is based on the concept of the ideal drug as a "magic bullet"; this became possible after techniques were developed for production of monoclonal antibodies (mAbs). Innovative DNA technologies have revolutionized this area and enhanced cli...
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PMID: 18693269
PDF is available here.
Abstract
We describe the new trifunctional antibody, Bi20 (FBTA05, anti-CD20 x anti-CD3), that connects B cells and T cells via its variable regions and recruits FcgammaRI(+) accessory immune cells via its Fc region. Bi20 mediated efficient and specific lysis of B-cell lines and of B cells with low CD20 expr...
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PMID: 18546289
PDF is available here.
Ralf Bargou,
Eugen Leo,
Gerhard Zugmaier,
Matthias Klinger,
Mariele Goebeler,
Stefan Knop,
Richard Noppeney,
Andreas Viardot,
Georg Hess,
Martin Schuler,
Hermann Einsele,
Christian Brandl,
Andreas Wolf,
Petra Kirchinger,
Petra Klappers,
Margit Schmidt,
Gert Riethmüller,
Carsten Reinhardt,
Patrick A Baeuerle and
Peter Kufer
Abstract
We report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non-Hodgkin's lymphoma patients led to an elimination...
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PMID: 18703743
PDF is available here.
Abstract
A total of 32/38 mice treated with BiLu and LAK splenocytes, were tumor-free survivors without GVHD for >200 days following inoculation of a 100% lethal tumor dose (5 x 10(4)). Of 28 disease-free surviving mice previously treated with LAK splenocytes and BiLu, 24 mice proved resistance to a second t...
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PMID: 18495330
PDF is available here.
Abstract
We examined whether a pretargeting method using a new recombinant anti-CD20 bispecific antibody (bsMAb) followed by (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid ((90)Y-DOTA)-peptide could reduce hematologic toxicity yet improve therapeutic responses compared with conventional...
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PMID: 18593929
PDF is available here.
Abstract
We have now examined the ability of a novel PAM4-based, bispecific monoclonal antibody (mAb) construct, TF10, to pretarget a radiolabeled peptide for improved imaging and therapy. TF10 is a humanized, bispecific mAb, divalent for mAb-PAM4 and monovalent for mAb-679, reactive against the histamine-su...
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PMID: 18559529
PDF is available here.
Abstract
Fresenius Biotech GmbH (licensed from TRION Pharma GmbH) is developing catumaxomab, a rat/murine hybrid, trifunctional, bispecific (anti-epithelial cell adhesion molecule and anti-CD3) mAb for the potential intravenous and intraperitoneal treatment of ovarian cancer, gastric cancer, malignant pleura...
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PMID: 18535935
PDF is available here.
Abstract
We show that the productivity of scFv against c-Met in Escherichia coli is significantly influenced by the orientation of its variable domains. We generated anti-c-Met scFv antibodies with two different domain orders (i.e., VL-linker-VH and VH-linker-VL), expressed them in the cytoplasm of E. coli t...
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PMID: 18600066
PDF is available here.
Abstract
We demonstrate here that a bispecific antibody incorporating a broadly reactive anti-gp41 antibody, F240, and an anti-IgA receptor (CD89) antibody is effective at directing neutrophils to destroy HIV. Not only are neutrophils the predominant type of white blood cells and very efficient at mediating...
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PMID: 18272577
PDF is available here.
Abstract
We have synthesized a library of bispecific Ab fragments to examine the effect of linking Kit with CD300a. In this study, we report that CD300a exerts a strong inhibitory effect on Kit-mediated SCF-induced signaling, consequently impairing MC differentiation, survival, and activation in vitro. This...
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PMID: 18424727
PDF is available here.
Abstract
Multiform single chain variable fragments (scFvs) including different length linker scFvs and bispecific scFv were constructed. The linker lengths of 0, 3, 5, 8, 12, and 15 amino acids between V(H) and V(L) of antideoxynivalenol (anti-DON) scFv were used to analyze the affinities of...
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PMID: 18499076
PDF is available here.
Abstract
We have investigated the effects of N-glycosylation on the activity and pharmacokinetics of a small bispecific single-chain diabody (scDb CEACD3) developed for the retargeting of cytotoxic T cells to CEA-expressing tumor cells. We could show that the introduction of N-glycosylation sequons into the...
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PMID: 18211902
PDF is available here.
Abstract
We have focused on producing the human 4-1BBL extracellular domain/anti-CD20 Fab' fusion protein. In this report, PCR and overlap PCR were used to construct the human 4-1BBL extracellular domain/anti-CD20 Fab' expression vector. DNA sequence was analyzed by the Terminus of Dideoxy Nucleotide. The pr...
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PMID: 18589811
PDF is available here.