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Antibody-dependent cellular toxicity

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https://www.readbyqxmd.com/read/29725332/improving-the-efficiency-of-v%C3%AE-9v%C3%AE-2-t-cell-immunotherapy-in-cancer
#1
REVIEW
Timm Hoeres, Manfred Smetak, Dominik Pretscher, Martin Wilhelm
Increasing immunological knowledge and advances in techniques lay the ground for more efficient and broader application of immunotherapies. gamma delta (γδ) T-cells possess multiple favorable anti-tumor characteristics, making them promising candidates to be used in cellular and combination therapies of cancer. They recognize malignant cells, infiltrate tumors, and depict strong cytotoxic and pro-inflammatory activity. Here, we focus on human Vγ9Vδ2 T-cells, the most abundant γδ T-cell subpopulation in the blood, which are able to inhibit cancer progression in various models in vitro and in vivo ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29723247/fc-engineering-of-anti-nectin-2-antibody-improved-thrombocytopenic-adverse-event-in-monkey
#2
Tsutomu Oshima, Hideaki Miyashita, Yoshimasa Ishimura, Yuki Ito, Yoko Tanaka, Akira Hori, Toshio Kokubo, Tomofumi Kurokawa
Nectin-2 is a transmembrane glycoprotein which is involved in the process of Ca2+-independent cell-cell adhesion. In our previous study, we have demonstrated that Nectin-2 is over-expressed in breast and ovarian cancer tissues by using gene expression analysis and immunohistochemistry. Furthermore, we discovered multiple anti-Nectin-2 fully human monoclonal antibodies which inhibited tumor growth in in vivo subcutaneous xenograft models with antibody-dependent cellular cytotoxicity (ADCC) as the principal mechanism of action...
2018: PloS One
https://www.readbyqxmd.com/read/29702148/immunomodulatory-effects-of-cd38-targeting-antibodies
#3
REVIEW
Niels W C J van de Donk
The fist in class CD38-targeting antibody, daratumumab, is currently approved as single agent and in combination with standards of care for the treatment of relapsed and refractory multiple myeloma. Based on the high activity and favorable toxicity profile of daratumumab, other CD38 antibodies, such as isatuximab, MOR202, and TAK-079, are being evaluated in MM and other malignancies. The CD38-targeting antibodies have classic Fc-dependent immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC)...
April 24, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29684562/bmt-following-non-myeloablative-treosulfan-conditioning-is-curative-in-a-murine-model-of-sickle-cell-disease
#4
Divya Devadasan, Chiao-Wang Sun, Erik R Westin, Li-Chen Wu, Kevin M Pawlik, Tim M Townes, Frederick D Goldman
Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for patients with sickle cell disease (SCD). However, morbidity associated with myeloablative conditioning and graft versus host disease has limited its utility. To this end, autologous HSCT for SCD using lentiviral gene-modified bone marrow (BM) or peripheral blood stem cells has been undertaken, though toxicities of fully ablative conditioning with busulfan and incomplete engraftment have been encountered. Treosulfan, a busulfan analog with a low extra-medullary toxicity profile, has been employed successfully as part of a myeloablative conditioning regimen in the allogeneic setting in SCD...
April 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29679372/paraneoplastic-cerebellar-degeneration-yo-antibody-alters-mitochondrial-calcium-buffering-capacity
#5
Debabrata Panja, Christian A Vedeler, Manja Schubert
AIM: Neurodegeneration is associated with dysfunction of calcium buffering capacity and thereby sustained cellular and mitochondrial calcium overload. Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neuron degeneration following paraneoplastic Yo antibody internalisation and binding to cerebellar degeneration-related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D28k malfunction. Therefore, we hypothesized that Yo antibody internalisation affects not only calbindin calcium binding capacity but also calcium-sensitive mitochondrial-associated signalling, causing mitochondrial calcium overload and thereby Purkinje neuron death...
April 21, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29651964/poly-l-arginine-enhancing-cytotoxicity-and-cellular-uptake-of-doxorubicin-and-necrotic-cell-death
#6
Bahareh Movafegh, Razieh Jalal, Zobeideh Mohammadi
OBJECTIVE: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. METHODS: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay...
April 11, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29609506/ublituximab-for-the-treatment-of-cd20-positive-b-cell-malignancies
#7
REVIEW
Hani M Babiker, Ashley E Glode, Laurence S Cooke, Daruka Mahadevan
Non-Hodgkin lymphoma (NHL) is the most common adult hematologic malignancy. Conventional methods of treatment are chemotherapy and radiation, which were associated with toxicities and lack of specificity. Potential cell surface targets for treatment of B-cell NHL (B-NHL) include CD19, CD20, and CD22 which are highly expressed on malignant B-cells. The development of monoclonal antibody (mAb) therapy directed against CD20 had the most clinical impact in the treatment of B-NHL. Early clinical trials with rituximab (RTX), the first chimeric mAb against CD20, showed efficacy and minimal toxicities...
April 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29531651/elotuzumab-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma-with-special-reference-to-its-modes-of-action-and-slamf7-signaling
#8
REVIEW
Masafumi Taniwaki, Mihoko Yoshida, Yosuke Matsumoto, Kazuho Shimura, Junya Kuroda, Hiroto Kaneko
Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29517616/a-dose-escalation-study-of-recombinant-human-interleukin-18-in-combination-with-ofatumumab-after-autologous-peripheral-blood-stem-cell-transplantation-for-lymphoma
#9
Michael J Robertson, Christopher W Stamatkin, David Pelloso, Jill Weisenbach, Nagendra K Prasad, Ahmad R Safa
Interleukin-18 (IL-18) is an immunostimulatory cytokine that augments antibody-dependent cellular cytotoxicity mediated by human natural killer cells against antibody-coated lymphoma cells in vitro and that has antitumor activity in animal models. Ofatumumab is a CD20 monoclonal antibody with activity against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20 lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29359469/p-and-e-selectin-receptor-antagonism-prevents-human-leukocyte-adhesion-to-activated-porcine-endothelial-monolayers-and-attenuates-porcine-endothelial-damage
#10
Christopher T Laird, Wessam Hassanein, Natalie A O'Neill, Beth M French, Xiangfei Cheng, William E Fogler, John L Magnani, Dawn Parsell, Arielle Cimeno, Carol J Phelps, David Ayares, Lars Burdorf, Agnes M Azimzadeh, Richard N Pierson
BACKGROUND: Alongside the need to develop more effective and less toxic immunosuppression, the shortage of human organs available for organ transplantation is one of the major hurdles facing the field. Research into xenotransplantation, as an alternative source of organs, has unveiled formidable challenges. Porcine lungs perfused with human blood rapidly sequester the majority of circulating neutrophils and platelets, which leads to inflammation and organ failure within hours, and is not significantly attenuated by genetic modifications to the pig targeted to diminish antibody binding and complement and coagulation cascade activation...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29325416/igy-reduces-afb-1-induced-cytotoxicity-cellular-dysfunction-and-genotoxicity-in-human-l-02-hepatocytes-and-swan-71-trophoblasts
#11
Taotao Qiu, Xing Shen, Zhen Tian, Riming Huang, Xiangmei Li, Juan Wang, Rong Wang, Yuanming Sun, Yiguo Jiang, Hongtao Lei, Huidong Zhang
Aflatoxin B1 (AFB1 ) causes hepatotoxic, genotoxic, and immunotoxic effects in a variety of species. Although various neutralizing agents of AFB1 toxicity have been studied, the egg yolk immunoglobulin (IgY) detoxification of small molecular toxins and the mechanisms underlying such effects have not yet been reported. In this investigation, anti-AFB1 IgY against AFB1 was successfully raised, and a competitive indirect enzyme-linked immunosorbent assay was established with a sensitive half-maximal inhibitory concentration (IC50, 2...
February 14, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29317395/the-role-of-elotuzumab-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#12
REVIEW
Jill M Comeau, Katherine Kelly, Gary W Jean
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy and safety, cost, and place in therapy of elotuzumab for treatment of relapsed or refractory multiple myeloma (MM) are reviewed. SUMMARY: Elotuzumab is a humanized monoclonal antibody that targets the signaling lymphocytic activation molecule (SLAM) protein SLAMF7 and facilitates an antibody-dependent cellular cytotoxicity interaction between myeloma cells and natural killer cells. Elotuzumab has U.S...
January 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29176838/inhibition-of-group-i-metabotropic-glutamate-receptors-protects-against-prion-toxicity
#13
Despoina Goniotaki, Asvin K K Lakkaraju, Amulya N Shrivastava, Pamela Bakirci, Silvia Sorce, Assunta Senatore, Rajlakshmi Marpakwar, Simone Hornemann, Fabrizio Gasparini, Antoine Triller, Adriano Aguzzi
Prion infections cause inexorable, progressive neurological dysfunction and neurodegeneration. Expression of the cellular prion protein PrPC is required for toxicity, suggesting the existence of deleterious PrPC-dependent signaling cascades. Because group-I metabotropic glutamate receptors (mGluR1 and mGluR5) can form complexes with the cellular prion protein (PrPC), we investigated the impact of mGluR1 and mGluR5 inhibition on prion toxicity ex vivo and in vivo. We found that pharmacological inhibition of mGluR1 and mGluR5 antagonized dose-dependently the neurotoxicity triggered by prion infection and by prion-mimetic anti-PrPC antibodies in organotypic brain slices...
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29141474/assessment-of-immunotoxicity-in-female-fischer-344-n-and-sprague-dawley-rats-and-female-b6c3f1-mice-exposed-to-hexavalent-chromium-via-the-drinking-water
#14
Kelly A Shipkowski, Christopher M Sheth, Matthew J Smith, Michelle J Hooth, Kimber L White, Dori R Germolec
Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29136037/safety-pharmacokinetics-and-immunological-activities-of-multiple-intravenous-or-subcutaneous-doses-of-an-anti-hiv-monoclonal-antibody-vrc01-administered-to-hiv-uninfected-adults-results-of-a-phase-1-randomized-trial
#15
RANDOMIZED CONTROLLED TRIAL
Kenneth H Mayer, Kelly E Seaton, Yunda Huang, Nicole Grunenberg, Abby Isaacs, Mary Allen, Julie E Ledgerwood, Ian Frank, Magdalena E Sobieszczyk, Lindsey R Baden, Benigno Rodriguez, Hong Van Tieu, Georgia D Tomaras, Aaron Deal, Derrick Goodman, Robert T Bailer, Guido Ferrari, Ryan Jensen, John Hural, Barney S Graham, John R Mascola, Lawrence Corey, David C Montefiori
BACKGROUND: VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. METHODS AND FINDINGS: HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29101107/cytokines-in-cancer-immunotherapy
#16
Thomas A Waldmann
Cytokines that control the immune response were shown to have efficacy in preclinical murine cancer models. Interferon (IFN)-α is approved for treatment of hairy cell leukemia, and interleukin (IL)-2 for the treatment of advanced melanoma and metastatic renal cancer. In addition, IL-12, IL-15, IL-21, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been evaluated in clinical trials. However, the cytokines as monotherapy have not fulfilled their early promise because cytokines administered parenterally do not achieve sufficient concentrations in the tumor, are often associated with severe toxicities, and induce humoral or cellular checkpoints...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29074301/identification-of-immune-biomarkers-related-to-disease-progression-and-treatment-efficacy-in-human-visceral-leishmaniasis
#17
Áquila S B Portela, Lourena E Costa, Beatriz C S Salles, Mariana P Lima, Thaís T O Santos, Fernanda F Ramos, Daniela P Lage, Vívian T Martins, Rachel B Caligiorne, Daniela R Lessa, Fabiana R Silva, Amanda S Machado, Guilherme F Nascimento, Isabela S Gama, Miguel A Chávez-Fumagalli, Antonio L Teixeira, Manoel O C Rocha, Regina L Rocha, Eduardo A F Coelho
Visceral leishmaniasis (VL) is a potentially fatal disease, in which the treatment based on chemotherapy is considered toxic. The cure of disease is associated with the life-long Th1-type immunity against the infection. The Th1-related cytokines production by peripheral blood mononuclear cells (PBMCs) seems to be crucial for host control of parasite load and clinical cure. In the current study, we used five proteins (IgE-dependent histamine-releasing factor [HRF], LiHyD, LiHyV, LiHyT and LiHyp6) recently shown to be antigenic and/or immunogenic in the canine VL, aiming to evaluate the antigen-specific antibody levels and cytokine production in PBMCs culture supernatants collected from VL patients before and after anti-VL treatment...
March 2018: Immunobiology
https://www.readbyqxmd.com/read/28992681/ofatumumab-monoclonal-antibody-affinity-maturation-through-in-silico-modeling
#18
Zahra Payandeh, Masoumeh Rajabibazl, Yousef Mortazavi, Azam Rahimpour, Amir Hossein Taromchi
Background: Ofatumumab, an anti-CD20 mAb, was approved in 2009 for the treatment of chronic lymphocytic leukemia. This mAb acts through immune-mediated mechanisms, in particular complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by natural killer cells as well as antibody-dependent phagocytosis by macrophages. Apoptosis induction is another mechanism of this antibody. Computational docking is the method of predicting the conformation of an antibody-antigen from its separated elements...
October 10, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28987943/a-standardized-extract-of-butea-monosperma-lam-flowers-suppresses-the-il-1%C3%AE-induced-expression-of-il-6-and-matrix-metalloproteases-by-activating-autophagy-in-human-osteoarthritis-chondrocytes
#19
Mohammad Y Ansari, Nazir M Khan, Tariq M Haqqi
BACKGROUND/OBJECTIVE: Osteoarthritis (OA) is a leading cause of joint dysfunction, disability and poor quality of life in the affected population. The underlying mechanism of joint dysfunction involves increased oxidative stress, inflammation, high levels of cartilage extracellular matrix degrading proteases and decline in autophagy-a mechanism of cellular defense. There is no disease modifying therapies currently available for OA. Different parts of the Butea monosperma (Lam.) plant have widely been used in the traditional Indian Ayurvedic medicine system for the treatment of various human diseases including inflammatory conditions...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28874561/localized-cd47-blockade-enhances-immunotherapy-for-murine-melanoma
#20
Jessica R Ingram, Olga S Blomberg, Jonathan T Sockolosky, Lestat Ali, Florian I Schmidt, Novalia Pishesha, Camilo Espinosa, Stephanie K Dougan, K Christopher Garcia, Hidde L Ploegh, Michael Dougan
CD47 is an antiphagocytic ligand broadly expressed on normal and malignant tissues that delivers an inhibitory signal through the receptor signal regulatory protein alpha (SIRPα). Inhibitors of the CD47-SIRPα interaction improve antitumor antibody responses by enhancing antibody-dependent cellular phagocytosis (ADCP) in xenograft models. Endogenous expression of CD47 on a variety of cell types, including erythrocytes, creates a formidable antigen sink that may limit the efficacy of CD47-targeting therapies...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
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