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Liposome antibodies

Taichi Kanzawa, Toshihito Hirai, Hironori Fukuda, Haruki Katsumata, Rumi Ishii, Masako Ikemiyagi, Yasuyuki Ishii, Kan Saiga, Masayoshi Okumi, Kazunari Tanabe
AIMS: Islet transplantation is an effective therapeutic option for type 1 diabetes. Although maintenance immunosuppression therapy is required to prevent allogeneic rejection and recurrence of autoimmunity, long-term allograft survival has not yet been achieved partly because of its adverse effects. The induction of donor-specific immunotolerance is a promising approach for long-term allograft survival without maintenance immunosuppression therapy. We previously reported that combination therapy using a liposomal ligand for invariant natural killer T cells, RGI-2001, and anti-CD154 antibody established mixed hematopoietic chimerism for the induction of donor-specific immunotolerance...
February 13, 2019: Acta Diabetologica
Xiaoyan Lu, Sha Liu, Meishan Han, Xiucheng Yang, Kaoxiang Sun, Hongbo Wang, Hongjie Mu, Yuan Du, Aiping Wang, Ling Ni, Chunyan Zhang
Afatinib, a selective and irreversible inhibitor of tyrosine kinase, was approved for the treatment of advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) overexpression in 2013. Cetuximab (CTX), an anti-EGFR monoclonal antibody, is co-administered with afatinib to improve efficacy. Unfortunately, dose-related adverse reactions caused by combination therapy have affected patient compliance, and have resulted in treatment discontinuation in severe cases. In the present study, afatinib was encapsulated in "liposomes" (LPs) to achieve longer circulation in the blood and an enhanced permeability-and-retention effect in tumors...
February 8, 2019: International Journal of Pharmaceutics
Victor U Weiss, Karin Wieland, Andreas Schwaighofer, Bernhard Lendl, Günter Allmaier
Gas-phase electrophoresis employing a nano Electrospray Differential Mobility Analyzer (nES DMA) aka Gas-phase Electrophoretic Mobility Molecular Analyzer (nES GEMMA) enables nanoparticle separation in the gas-phase according to their surface-dry diameter with number-based detection. Moreover, particles in the nanometer size range can be collected after size-selection on supporting materials. It has been shown by subsequent analyses employing orthogonal methods, for instance microscopic or antibody-based techniques, that the surface integrity of collected analytes remains intact...
February 8, 2019: Analytical Chemistry
Junru Cui, Caitlin M O'Connell, Antonio Costa, Yan Pan, Joan A Smyth, Paulo H Verardi, Diane J Burgess, Herbert J Van Kruiningen, Antonio E Garmendia
Porcine reproductive and respiratory syndrome virus (PRRSV), is a highly mutable RNA virus that affects swine worldwide and its control is very challenging due to its formidable heterogeneity in the field. In the present study, DNA vaccines constructed with PRRSV GP5-Mosaic sequences were complexed to cationic liposomes and administered to experimental pigs by intradermal and intramuscular injection, followed by three boosters 14, 28 and 42 days later. The GP5-Mosaic vaccine thus formulated was immunogenic and induced protection from challenge in vaccinated pigs comparable to that induced by a wild type (VR2332) GP5 DNA vaccine (GP5-WT)...
2019: PloS One
Esther Frohnmeyer, Nadine Tuschel, Tobias Sitz, Cornelia Hermann, Gregor T Dahl, Florian Schulz, Antje J Baeumner, Markus Fischer
Aptamers are envisioned to serve as powerful synthetic substitutes to antibodies in a variety of bioanalytical assay formats. However, lateral flow assays (LFAs) remain dominated by antibody-based strategies. In this study, a LFA for the detection of cholera toxin as a model analyte is developed and optimized using a synthetic aptamer and a naturally occurring receptor as biorecognition elements and directly compared with solely aptamer and aptamer and antibody-based alternative approaches. The aptamer (CT916) recently selected by our group, GM1 receptors and an anti-cholera toxin antibody were evaluated...
January 25, 2019: Analyst
Steffen Wöll, Stephan Dickgiesser, Nicolas Rasche, Stefan Schiller, Regina Scherließ
PURPOSE: Conventional chemotherapy is associated with therapy-limiting side effects, which might be alleviated by targeted chemotherapeutics such as immunoliposomes. The targeting ligands of immunoliposomes are commonly attached by unspecific chemical conjugation, bearing risk of structural heterogeneity and therewith related biological consequences. Chemoenzymatic methods may mitigate such risks through site-specific conjugation. METHODS: The formulation parameters for pentaglycine-modified, doxorubicin-loaded liposomes and the reaction conditions for a site-specific, Sortase-A mediated conjugation with monoclonal antibodies were thoroughly evaluated...
January 21, 2019: European Journal of Pharmaceutics and Biopharmaceutics
Ragab M Fereig, Hanan H Abdelbaky, Yasuhiro Kuroda, Yoshifumi Nishikawa
Neospora caninum is an intracellular protozoan parasite closely related to Toxoplasma gondii. N. caninum is thought to be a major cause of abortion in cattle worldwide. Given the current situation of drastic economic losses and a lack of efficient control strategies against such parasites, the challenge to develop potent vaccine candidates and technologies remains. We investigated the immune stimulating activity of N. caninum cyclophilin (NcCyp) with and without a formulation with oligomannose-coated-liposomes (OML) as the potential adjuvant...
January 16, 2019: Vaccine
María Merino, Ana Contreras, Noelia Casares, Iñaki Troconiz, Timo Lm Ten Hagen, Pedro Berraondo, Sara Zalba, María J Garrido
Immunoliposomes (ILs), obtained with monoclonal antibodies (mAbs) decorating the liposome surface, are used for cancer treatment. These mAbs provide the recognition of molecules upregulated in cancer cells, like Programmed Death-Ligand 1 (PD-L1), an immune-checkpoint involved in tumor resistance, forming a complex that blocks this molecule and thereby, induces antitumor immune response. This mechanism introduces a new concept for ILs. ILs coupled to anti-PD-L1 or its Fab' fragment have been developed and in vitro/in vivo characterized...
January 14, 2019: Nanomedicine: Nanotechnology, Biology, and Medicine
Nancy Dumont, Samantha Merrigan, Jason Turpin, Cynthia Lavoie, Vasilios Papavasiliou, Elena Geretti, Christopher Espelin, Lia Luus, Walid Kamoun, Omid Ghasemi, G Gary Sahagian, William Muller, Bart Hendriks, Thomas J Wickham, Daryl C Drummond
MM-302 is an anti-HER2 antibody-targeted pegylated liposomal doxorubicin designed to deliver doxorubicin specifically to HER2-expressing solid tumors. The delivery and activity of MM-302 was evaluated in orthotopic, transgenic, and intravenous breast cancer models expressing varying levels of HER2 that metastasize to some of the most common sites of dissemination for breast cancer, namely, lung, liver, and brain. Metastatic burden was quantified by gross evaluation, immunohistochemistry (IHC), and bioluminescent imaging...
January 14, 2019: Nanomedicine: Nanotechnology, Biology, and Medicine
Jan Philipp Bewersdorf, Maximilian Stahl, Amer M Zeidan
The 5-year overall survival rate of AML patients remains 25-40%. The prognosis is even more dismal for older patients who are ineligible for intensive chemotherapy and patients with secondary or relapsed/refractory AML. In 2017, 4 new drugs were approved by the US Food and Drug Administration for AML treatment: The FLT3 inhibitor midostaurin, the isocitrate dehydrogenase (IDH)-2 inhibitor enasidenib, a liposomal formulation of cytarabine and daunorubicin (CPX-351), and the anti-CD33 antibody gemtuzumab ozogamicin...
January 17, 2019: Leukemia & Lymphoma
Shanni Hong, Pi Ding, Yu Luo, Tian Gao, Ye Zhang, Renjun Pei
A novel bispecific α-Gal liposome was constructed by self-assembling AS1411 aptamers into the α-Gal containing liposomes. The α-Gal liposomes were prepared using cell membranes of red blood cells from rabbit, which are composed of cholesterol, phospholipids, and α-Gal glycolipids. AS1411 is a DNA aptamer with high specificity and affinity for nucleolin and could integrate into liposomes by the modification of cholesterol. The bispecific α-Gal liposomes surface-functionalized by α-Gal and AS1411 aptamer could recognize anti-Gal antibodies and nucleolin overexpressed by tumor cells simultaneously, followed by activating the immune system to attack the tumor cells, resulting in the lysis of the tumor cells by antibody dependent cell-mediated cytotoxicity...
January 16, 2019: Journal of Biomedical Materials Research. Part A
D Scott Wilson, Sachiko Hirosue, Michal M Raczy, Leonardo Bonilla-Ramirez, Laura Jeanbart, Ruyi Wang, Marcin Kwissa, Jean-Francois Franetich, Maria A S Broggi, Giacomo Diaceri, Xavier Quaglia-Thermes, Dominique Mazier, Melody A Swartz, Jeffrey A Hubbell
Fully effective vaccines for complex infections must elicit a diverse repertoire of antibodies (humoral immunity) and CD8+ T-cell responses (cellular immunity). Here, we present a synthetic glyco-adjuvant named p(Man-TLR7), which, when conjugated to antigens, elicits robust humoral and cellular immunity. p(Man-TLR7) is a random copolymer composed of monomers that either target dendritic cells (DCs) via mannose-binding receptors or activate DCs via Toll-like receptor 7 (TLR7). Protein antigens are conjugated to p(Man-TLR7) via a self-immolative linkage that releases chemically unmodified antigen after endocytosis, thus amplifying antigen presentation to T cells...
January 14, 2019: Nature Materials
Morten Nørgaard Andersen, Anders Etzerodt, Jonas H Graversen, Lisa C Holthof, Søren K Moestrup, Marianne Hokland, Holger J Møller
Tumor-associated macrophages (TAMs) are of major importance in cancer-related immune suppression, and tumor infiltration by CD163pos TAMs is associated with poor outcome in most human cancers. Therefore, therapeutic strategies for reprogramming TAMs from a tumor-supporting (M2-like) phenotype towards a tumoricidal (M1-like) phenotype are of great interest. Activation of the transcription factor STAT3 within the tumor microenvironment is associated with worse prognosis, and STAT3 activation promotes the immunosuppressive phenotype of TAMs...
January 14, 2019: Cancer Immunology, Immunotherapy: CII
Zahra Moradpour, Leila Barghi
Epidermal growth factor receptors (EGFRs) have potential to be considered as therapeutic target for cancer treatment especially in cancer patients with overexpression of EGFR. Cetuximab as a first monoclonal antibody and Imatinib as the first small molecule tyrosine kinase inhibitor (SMTKI) were approved by FDA in 1998 and 2001. About 28 SMTKIs have been approved until 2015 and a large number of compound with kinase inhibitory activity are at the different phases of clinical trials. Although Kinase inhibitors target specific intracellular pathways, their tissue or cellular distribution are not specific...
2019: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Man Li, Yuting Yang, Chaoqun Xu, Jiaojie Wei, Yingke Liu, Xingli Cun, Qianwen Yu, Xian Tang, Sheng Yin, Zhirong Zhang, Qin He
Chemoimmunotherapy with chemotherapeutics and immunoadjuvant inhibits tumor growth by activating cytotoxic T cells. However, this process also upregulates the expression of PD-1/PD-L1 and consequently leads to immune suppression. To maximize the anti-tumor immune responses and alleviate immunosuppression, PD-L1 antibody was combined with paclitaxel (PTX) and the immunoadjuvant α-galactosylceramide (αGC), which were coencapsulated into pH-sensitive TH peptide-modified liposomes (PTX/αGC/TH-Lip) to treat melanoma and lung metastasis...
January 11, 2019: AAPS Journal
Kasper Bendix Johnsen, Martin Bak, Fredrik Melander, Maj Schneider Thomsen, Annette Burkhart, Paul Joseph Kempen, Thomas Lars Andresen, Torben Moos
Transport of the majority of therapeutic molecules to the brain is precluded by the presence of the blood-brain barrier (BBB) rendering efficient treatment of many neurological disorders impossible. This BBB, nonetheless, may be circumvented by targeting receptors and transport proteins expressed on the luminal surface of the brain capillary endothelial cells (BCECs). The transferrin receptor (TfR) has remained a popular target since its original description for this purpose, although clinical progression of TfR-targeted drug constructs or nanomedicines remains unsuccessful...
January 8, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Benjamin Mordmüller, Mihály Sulyok, Diane Egger-Adam, Mafalda Resende, Willem A de Jongh, Mette H Jensen, Helle Holm Smedegaard, Sisse B Ditlev, Max Soegaard, Lars Poulsen, Charlotte Dyring, Carlos Lamsfus Calle, Annette Knoblich, Javier Ibáñez, Meral Esen, Philippe Deloron, Nicaise Ndam, Saadou Issifou, Sophie Houard, Randall F Howard, Steven G Reed, Odile Leroy, Adrian J F Luty, Thor G Theander, Peter G Kremsner, Ali Salanti, Morten A Nielsen
Background: Malaria in pregnancy has major impacts on mother and child health. The current strategy to prevent pregnancy-associated malaria (PAM) comprises intermittent preventive treatment and use of impregnated bednets. To complement existing interventions, we developed a malaria vaccine candidate aiming at reducing sequestration of asexual "blood-stage" parasites in the placenta, the major virulence mechanism in PAM. Methods: PAMVAC is a vaccine candidate based on a recombinant fragment of VAR2CSA, the Plasmodium falciparum protein responsible for binding to the placenta via chondroitin sulfate A (CSA)...
January 10, 2019: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Yalong Wang, Huizhi Huang, Haijuan Zou, Xuyan Tian, Jun Hu, Pengxin Qiu, Haiyan Hu, Guangmei Yan
Oncolytic viral therapy is an attractive novel strategy for cancer therapy. As a natural alphavirus, oncolytic virus M1 is able to infect and kill various zinc finger antiviral protein (ZAP)-deficient tumor cells selectively, while leaving normal cells undamaged. However, M1 can trigger the production of neutralizing antibodies that dramatically weaken its antitumor effect. In order to attenuate immunogenicity of therapeutic M1 virus, we encapsulated it into liposomes (referred to as M-LPO) using the thin-film hydration method...
January 3, 2019: Molecular Pharmaceutics
Fengling Wang, Xi Ye, Yifan Wu, Huihui Wang, Chengming Sheng, Daiyin Peng, Weidong Chen
Repeated injection of PEGylated liposomes can cause the disappearance of long circulating property because of the induction of anti-PEG IgM antibody referred to as "accelerated blood clearance (ABC) phenomenon." Although ABC phenomenon typically occurs when entrapped drugs are chemotherapeutic agent with low cytotoxic, there is little evidence of accelerated blood clearance of PEGylated herbal-derived compound on repeated injection. Herein, we investigated the blood concentration of PEGylated liposomal gambogenic acid (PEG-GEA-L), a model PEGylated liposomal herbal extract, on its repeated injection to rats...
January 2019: Journal of Pharmaceutical Sciences
William P McGuire, Richard T Penson, Martin Gore, Antonio Casado Herraez, Patrick Peterson, Ashwin Shahir, Robert Ilaria
BACKGROUND: Olaratumab is a platelet-derived growth factor receptor-α (PDGFRα)-targeting monoclonal antibody blocking PDGFRα signaling. PDGFRα expression is associated with a more aggressive phenotype and poor ovarian cancer outcomes. This randomized, open label phase II study evaluated olaratumab plus liposomal doxorubicin compared with liposomal doxorubicin alone in advanced ovarian cancer patients. METHODS: Patients with platinum-refractory or platinum-resistant advanced ovarian cancer were randomized 1:1 to receive liposomal doxorubicin (40 mg/m2 , intravenous infusion) administered every 4 weeks with or without olaratumab (20 mg/kg, IV infusion) every 2 weeks...
December 27, 2018: BMC Cancer
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