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https://www.readbyqxmd.com/read/27913998/immunotherapy-for-breast-cancer-past-present-and-future
#1
Alison Spellman, Shou-Ching Tang
Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment. Increasing efficacy of these treatments in breast cancer patients requires identification of better biomarkers to guide patient selection; recognizing when to initiate these therapies in multi-modality treatment plans; establishing novel assays to monitor immune-mediated responses; and creating combined systemic therapy options incorporating conventional treatments such as chemotherapy and endocrine therapy...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913544/treatment-of-rare-factor-deficiencies-in-2016
#2
Flora Peyvandi, Marzia Menegatti
Rare bleeding disorders (RBDs) are a heterogeneous group of coagulation disorders characterized by fibrinogen, prothrombin, factors V, VII, X, XI, or XIII (FV, FVII, FX, FXI, or FXIII, respectively), and the combined factor V + VIII and vitamin K-dependent proteins deficiencies, representing roughly 5% of all bleeding disorders. They are usually transmitted as autosomal, recessive disorders, and the prevalence of the severe forms could range from 1 case in 500 000 for FVII up to 1 in 2-3 million for FXIII in the general population...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27870103/role-of-immunotherapy-in-targeting-the-bone-marrow-microenvironment-in-multiple-myeloma-an-evolving-therapeutic-strategy
#3
Clement Chung
Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor...
November 21, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27836687/integrated-bio-affinity-nano-platform-into-a-microfluidic-immunosensor-based-on-monoclonal-bispecific-trifunctional-antibodies-for-the-electrochemical-determination-of-epithelial-cancer-biomarker
#4
Karina Bravo, Francisco G Ortega, Germán A Messina, María I Sanz, Martín A Fernández-Baldo, Julio Raba
BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is a biomarker that is highly overexpressed on the surface of epithelial carcinoma cells. In this study, silver nanoparticles covered with polyvinyl alcohol (AgNPs-PVA) were synthesized, characterized and used in a microfluidic immunosensor based on the use of anti-EpCAM recombinant antibodies as a trapping agent. METHODS: The concentration of trapped EpCAM is then electrochemically quantified by HRP-conjugated anti-EpCAM-antibody...
November 9, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27820973/emerging-biological-therapies-to-treat-acute-lymphoblastic-leukemia
#5
Françoise Huguet, Suzanne Tavitian
Various settings of acute lymphoblastic leukemia (ALL) represent unmet medical needs: first remission at high risk of relapse, such as persistent minimal residual disease (MRD); relapse/refractoriness (R/R); elderly patients. Biological therapies targeting widely-shared antigens of blast cells have entered the clinic in B-cell precursor (BCP)-ALL. Area covered. Results of phase II/III trials of monoclonal antibodies (MoAbs) and phase I/II trials of adoptive cell therapy by chimeric antigen receptor-engineered T cells (CAR-T cells) are presented...
November 8, 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27792681/distinct-hiv-1-neutralization-potency-profiles-of-ibalizumab-based-bispecific-antibodies
#6
Ruijiang Song, Craig Pace, Michael S Seaman, Qing Fang, Ming Sun, Chasity D Andrews, Amos Wu, Neal N Padte, David D Ho
BACKGROUND: Preexposure prophylaxis using antiretroviral agents has been shown to effectively prevent human immunodeficiency virus type 1 (HIV-1) acquisition in high-risk populations. However, the efficacy of these regimens is highly variable, which is thought to be largely due to the varying degrees of adherence to a daily intervention in the populations. Passive immunization using broadly neutralizing antibodies (bNAbs) against HIV-1, with their relatively long half-life and favorable safety profile, could provide an alternative to daily preexposure prophylaxis...
December 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/27786606/bispecific-antibodies-for-viral-immunotherapy
#7
Elisabeth K Nyakatura, Alexandra Y Soare, Jonathan R Lai
Bispecific antibody engineering, in which binding specificities toward two distinct epitopes are combined into a single molecule, can greatly enhance immunotherapeutic properties of monoclonal antibodies. While the bispecific antibody approach has been applied widely to targets for indications such as cancer and inflammation, the development of such agents for viral immunotherapy is only now emerging. Here, we review recent advances in the development of bispecific antibodies for viral immunotherapy, highlighting promising in vitro and in vivo results...
October 27, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27747522/emerging-therapies-for-rheumatoid-arthritis
#8
Joachim R Kalden
Diverse strategies to develop novel treatments for rheumatoid arthritis which specifically target those patients who do not respond to available medications, including biologics, are currently being explored. New potential therapeutic approaches which may become available as part of standard therapeutic regimens include the propagation of regulatory T cells and-in the future-of regulatory B cells. New biologic disease-modifying antirheumatic drugs (b-DMARDs) against interleukin-17 and -6, granulocyte-macrophage colony-stimulating factor, and complement component 5 are now standard components of clinical treatment programs...
June 2016: Rheumatol Ther
https://www.readbyqxmd.com/read/27746780/recent-progress-toward-engineering-hiv-1-specific-neutralizing-monoclonal-antibodies
#9
Ming Sun, Yue Li, Huiwen Zheng, Yiming Shao
The recent discoveries of broadly potent neutralizing human monoclonal antibodies represent a new generation of antiretrovirals for the treatment and prophylaxis. Antibodies are generally considered more effective and safer and have been proved to provide passive protection against mucosal challenge in humanized mice and macaques. Several neutralizing Abs could protect animals against HIV-1 but are not effective when used in an established infected model for therapy. In order to overcome the limitation of antiviral activities, multiple antibody-engineering technologies have been explored to generate "the better" neutralizing antibodies against HIV-1 since bNAbs attack viral entry by various mechanisms...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27742718/targeting-key-angiogenic-pathways-with-a-bispecific-crossmab-optimized-for-neovascular-eye-diseases
#10
Jörg T Regula, Peter Lundh von Leithner, Richard Foxton, Veluchamy A Barathi, Chui Ming Gemmy Cheung, Sai Bo Bo Tun, Yeo Sia Wey, Daiju Iwata, Miroslav Dostalek, Jörg Moelleken, Kay G Stubenrauch, Everson Nogoceke, Gabriella Widmer, Pamela Strassburger, Michael J Koss, Christian Klein, David T Shima, Guido Hartmann
Anti-angiogenic therapies using biological molecules that neutralize vascular endothelial growth factor-A (VEGF-A) have revolutionized treatment of retinal vascular diseases including age-related macular degeneration (AMD). This study reports preclinical assessment of a strategy to enhance anti-VEGF-A monotherapy efficacy by targeting both VEGF-A and angiopoietin-2 (ANG-2), a factor strongly upregulated in vitreous fluids of patients with retinal vascular disease and exerting some of its activities in concert with VEGF-A...
November 2, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27725635/envelope-specific-antibodies-and-antibody-derived-molecules-for-treating-and-curing-hiv-infection
#11
Guido Ferrari, Barton F Haynes, Scott Koenig, Jeffrey L Nordstrom, David M Margolis, Georgia D Tomaras
HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. Upon reactivation of proviral gene expression, HIV-1 envelope (HIV-1 Env) glycoproteins are expressed on the cell surface, transforming latently infected cells into targets for HIV-1 Env-specific monoclonal antibodies (mAbs), which can engage immune effector cells to kill productively infected CD4(+) T cells and thus limit the spread of progeny virus...
October 7, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27706938/bispecific-monoclonal-antibody-based-multi-analyte-elisa-for-furaltadone-metabolite-malachite-green-and-leucomalachite-green-in-aquatic-products
#12
Feng Wang, Hong Wang, Yudong Shen, Yongjun Li, Jie-Xian Dong, Zhenlin Xu, Jinyi Yang, Yuanming Sun, Zhili Xiao
A new multi-analyte immunoassay was designed to screen furaltadone metabolite 5-morpholinomethyl-3-amino-2-oxazolidone (AMOZ), malachite green (MG), and leucomalachite green (LMG) in aquatic products using a bispecific monoclonal antibody (BsMAb). Gradient drug mutagenesis methods were separately used to prepare an anti-3-nitrobenzaldehyde-derivatized AMOZ (3-NPAMOZ) hybridoma cell line that was hypoxanthine-guanine-phosphoribosyltransferase (HGRPT) deficient and an anti-LMG hybridoma cell line that was thymidine kinase (TK) deficient...
October 5, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27697033/recombinant-antibody-fragments-for-neurodegenerative-diseases
#13
Karen Manoutcharian, Roxanna Perez-Garmendia, Goar Gevorkian
Recombinant antibody fragments are promising alternatives to full-length immunoglobulins and offer important advantages compared with conventional monoclonal antibodies: extreme specificity, higher affinity, superior stability and solubility, reduced immunogenicity as well as easy and inexpensive large-scale production. Different antibody formats such as single-chain fragment variable (scFv), single-domain antibody fragments (VHHs or sdAbs), bispecific antibodies (bsAbs), intrabodies and nanobodies, are currently being studied in pre-clinical models of cancer as well as infectious and autoimmune diseases and many of them are being tested as therapeutics in clinical trials...
September 30, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27680183/an-efficient-route-to-bispecific-antibody-production-using-single-reactor-mammalian-co-culture
#14
Whitney Shatz, Domingos Ng, George Dutina, Athena W Wong, Diana Ronai Dunshee, Junichiro Sonoda, Amy Shen, Justin M Scheer
Bispecific antibodies have shown promise in the clinic as medicines with novel mechanisms of action. Lack of efficient production of bispecific IgGs, however, has limited their rapid advancement. Here, we describe a single-reactor process using mammalian cell co-culture production to efficiently produce a bispecific IgG with four distinct polypeptide chains without the need for parallel processing of each half-antibody or additional framework mutations. This method resembles a conventional process, and the quality and yield of the monoclonal antibodies are equal to those produced using parallel processing methods...
September 28, 2016: MAbs
https://www.readbyqxmd.com/read/27608667/a-trojan-horse-bispecific-antibody-strategy-for-broad-protection-against-ebolaviruses
#15
Anna Z Wec, Elisabeth K Nyakatura, Andrew S Herbert, Katie A Howell, Frederick W Holtsberg, Russell R Bakken, Eva Mittler, John R Christin, Sergey Shulenin, Rohit K Jangra, Sushma Bharrhan, Ana I Kuehne, Zachary A Bornholdt, Andrew I Flyak, Erica Ollmann Saphire, James E Crowe, M Javad Aman, John M Dye, Jonathan R Lai, Kartik Chandran
There is an urgent need for monoclonal antibody (mAb) therapies that broadly protect against Ebola virus and other filoviruses. The conserved, essential interaction between the filovirus glycoprotein, GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs but is shielded by multiple mechanisms, including physical sequestration in late endosomes. Here, we describe a bispecific-antibody strategy to target this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mAb against a conserved, surface-exposed GP epitope...
October 21, 2016: Science
https://www.readbyqxmd.com/read/27578890/tetramabs-simultaneous-targeting-of-four-oncogenic-receptor-tyrosine-kinases-for-tumor-growth-inhibition-in-heterogeneous-tumor-cell-populations
#16
Raffaella Castoldi, Jürgen Schanzer, Christian Panke, Ute Jucknischke, Natalie J Neubert, Rebecca Croasdale, Werner Scheuer, Johannes Auer, Christian Klein, Gerhard Niederfellner, Sebastian Kobold, Claudio Sustmann
Monoclonal antibody-based targeted tumor therapy has greatly improved treatment options for patients. Antibodies against oncogenic receptor tyrosine kinases (RTKs), especially the ErbB receptor family, are prominent examples. However, long-term efficacy of such antibodies is limited by resistance mechanisms. Tumor evasion by a priori or acquired activation of other kinases is often causative for this phenomenon. These findings led to an increasing number of combination approaches either within a protein family, e...
October 2016: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/27568879/tumour-cell-surface-antigen-targeted-therapies-in-b-cell-lymphomas-beyond-rituximab
#17
Matthew Ku, Geoff Chong, Eliza A Hawkes
Recent proliferation of novel targeted therapies in lymphoma has been substantial. B-cell receptor pathway inhibitors and immune checkpoint inhibitors have been a major focus, however significant advances in monoclonal antibodies (MoAbs) which directly target malignant cells have also occurred. These MoAbs continue to make significant impact in lymphoma management. Novel dosing schedules of anti-CD20 MoAb rituximab potentially optimise efficacy in specific lymphoma subgroups, as certain populations may be receiving suboptimal doses using current schedules...
August 12, 2016: Blood Reviews
https://www.readbyqxmd.com/read/27552846/resubmission-fc-engineering-to-improve-the-function-of-therapeutic-antibodies
#18
Futa Mimoto, Taichi Kuramochi, Hitoshi Katada, Tomoyuki Igawa, Kunihiro Hattori
Monoclonal antibodies are currently the most attractive therapeutic modality in a broad range of disease areas, including infectious diseases, autoimmune diseases, and oncology. Fc engineering is one attractive application to maximize the value or overcome the drawbacks of monoclonal antibodies for therapeutic use. With the Fc region, antibodies bind to several types of receptors, such as Fc gamma receptors, a complement receptor, and a neonatal Fc receptor. Through this interaction with the receptors, antibodies demonstrate unique functions, such as antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, complement dependent cytotoxicity, agonistic activity, and endosomal recycling...
August 24, 2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/27546726/dual-anti-idiotypic-purification-of-a-novel-native-format-biparatopic-anti-met-antibody-with-improved-in-vitro-and-in-vivo-efficacy
#19
Marie Godar, Virginia Morello, Ava Sadi, Anna Hultberg, Natalie De Jonge, Cristina Basilico, Valérie Hanssens, Michael Saunders, Bart N Lambrecht, Mohamed El Khattabi, Hans de Haard, Paolo Michieli, Christophe Blanchetot
Bispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27525074/blinatumomab-may-induce-graft-versus-host-leukemia-in-patients-with-pre-b-all-relapsing-after-hematopoietic-stem-cell-transplant
#20
Muhammad Waqas Khan, Zartash Gul
Blinatumomab, a bispecific T-cell engager monoclonal antibody used to manage Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) can be used to treat patients by inducing graft versus leukemia reaction post allogeneic hematopoietic stem cell transplantation, a feature which it was post allogeneic bone marrow transplantation, a feature which this drug was not aimed to do.
August 2016: Clinical Case Reports
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