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Antibody dependent cellular cytotoxicity

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https://www.readbyqxmd.com/read/29241186/strengthening-gastric-cancer-therapy-by-trastuzumab-conjugated-nanoparticles-with-simultaneous-encapsulation-of-anti-mir-21-and-5-fluorouridine
#1
Nan Hu, Jun Feng Yin, Ze Ji, Yidong Hong, Puyuan Wu, Baoxiang Bian, Ziyan Song, Rutian Li, Qin Liu, Fenglei Wu
BACKGROUND/AIMS: MicroRNA-21 is an oncogenic miR (oncomiR) frequently elevated in gastric cancer (GC). Overexpression of miR-21 decreases the sensitivity of GC cells to 5-fluorouridine (5-Fu) and trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including anti-miRNA oligonucleotides (AMOs). This study is a continuation of earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target GC with HER2 receptor over-expression using anti-miRNA-21 (AMO-21) and 5-Fu...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29239894/temporal-variation-in-hiv-specific-igg-subclass-abs-during-acute-infection-differentiates-spontaneous-controllers-from-chronic-progressors
#2
Saheli Sadanand, Jishnu Das, Amy W Chung, Matthew K Schoen, Sophie Lane, Todd J Suscovich, Hendrik Streeck, Davey Smith, Susan Little, Douglas A Lauffenburger, Douglas Richman, Galit Alter
OBJECTIVE: Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between subjects who ultimately became controllers versus those who became progressors. METHODS: IgG was purified from plasma from nine acutely infected subjects who subsequently controlled HIV spontaneously (controllers) and ten acutely infected individuals who did not control viremia (progressors)...
December 12, 2017: AIDS
https://www.readbyqxmd.com/read/29223828/rationale-for-combination-of-therapeutic-antibodies-targeting-tumor-cells-and-immune-checkpoint-receptors-harnessing-innate-and-adaptive-immunity-through-igg1-isotype-immune-effector-stimulation
#3
REVIEW
Robert L Ferris, Heinz-Josef Lenz, Anna Maria Trotta, Jesús García-Foncillas, Jeltje Schulten, François Audhuy, Marco Merlano, Gerard Milano
Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies...
December 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29209323/non-neutralizing-antibodies-directed-against-hiv-and-their-functions
#4
REVIEW
Luzia M Mayr, Bin Su, Christiane Moog
B cells produce a plethora of anti-HIV antibodies (Abs) but only few of them exhibit neutralizing activity. This was long considered a profound limitation for the enforcement of humoral immune responses against HIV-1 infection, especially since these neutralizing Abs (nAbs) are extremely difficult to induce. However, increasing evidence shows that additional non-neutralizing Abs play a significant role in decreasing the viral load, leading to partial and sometimes even total protection. Mechanisms suspected to participate in protection are numerous...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29194123/anti-hiv-1-antibody-dependent-cellular-cytotoxicity-is-there-more-to-antibodies-than-neutralization
#5
Wen Shi Lee, Stephen J Kent
PURPOSE OF REVIEW: An increasing body of evidence suggests that nonneutralizing Fc effector functions including antibody-dependent cellular cytotoxicity (ADCC) contribute to protection against HIV-1 acquisition. We discuss recent advances in anti-HIV-1 ADCC research with a particular focus on ADCC mediated by Env-specific antibodies in vitro and in vivo, the curative potential of HIV-1-specific ADCC antibodies and the mechanisms of HIV-1 resistance to ADCC. RECENT FINDINGS: ADCC activities of broadly neutralizing and nonneutralizing monoclonal antibody panels were recently characterized in vitro against several lab-adapted and primary isolates of HIV-1...
November 30, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29187584/a-novel-bispecific-c-met-ctla-4-antibody-targeting-lung-cancer-stem-cell-like-cells-with-therapeutic-potential-in-human-non-small-cell-lung-cancer
#6
Jian-Feng Li, Yuan-Yuan Niu, Yan-Li Xing, Feng Liu
A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) growth is driven by lung cancer stem cell-like cells (LCSCs), but here are still not any effective strategies to remove LCSCs. The bispecific antibody is a novel antibody, which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. Here, we designed and synthesized a new bispecific antibody (BsAb), BsAb-5, that can target cellular-mesenchymal to epithelial transition factor (c-MET) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in CD166+ LCSCs with high affinity and specificity, for the first time...
November 29, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29187404/lsr-antibody-therapy-inhibits-ovarian-epithelial-tumor-growth-by-inhibiting-lipid-uptake
#7
Kosuke Hiramatsu, Satoshi Serada, Takayuki Enomoto, Yusuke Takahashi, Satoshi Nakagawa, Satoshi Nojima, Akiko Morimoto, Shinya Matsuzaki, Takuhei Yokoyama, Tsuyoshi Takahashi, Minoru Fujimoto, Hiroshi Takemori, Yutaka Ueda, Kiyoshi Yoshino, Eiichi Morii, Tadashi Kimura, Tetsuji Naka
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy but it still lacks effective treatment options. In this study, we utilized proteomic technology to identify lipolysis-stimulated lipoprotein receptor (LSR) as a new tumor antigen of EOC. Immunohistochemical analysis of EOC tissues in conjunction with survival analysis of EOC patients showed that high expression of LSR is associated with poor prognosis. High LSR expression also occurred in tumor metastases including to the lymph node and omentum...
November 29, 2017: Cancer Research
https://www.readbyqxmd.com/read/29181155/comparison-of-the-effect-of-the-aerobic-glycolysis-inhibitor-dichloroacetate-and-of-the-krebs-cycle-inhibitor-lw6-on-cellular-and-humoral-alloimmunity
#8
Theodoros Eleftheriadis, Georgios Pissas, Athanasios Mavropoulos, Vassilios Liakopoulos, Ioannis Stefanidis
Cell metabolism is altered during T-cell and B-cell activation and differentiation. Clarifying the exact metabolic shifts may lead to the development of new immunosuppressive medications. In this study, the effect of the aerobic glycolysis inhibitor dichloroacetate (DCA) and of the Krebs cycle enzyme malate dehydrogenase 2 (MDH2) inhibitor LW6 on T-cell alloimmune clonal expansion and on alloantibody production, was evaluated. T-cell clonal expansion was assessed in two-way mixed lymphocyte reaction (MLR). Humoral alloimmunity was evaluated by the alloantibody production in one-way MLR...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29181007/interplay-between-natural-killer-cells-and-anti-her2-antibodies-perspectives-for-breast-cancer-immunotherapy
#9
REVIEW
Aura Muntasell, Mariona Cabo, Sonia Servitja, Ignasi Tusquets, María Martínez-García, Ana Rovira, Federico Rojo, Joan Albanell, Miguel López-Botet
Overexpression of the human epidermal growth factor receptor 2 (HER2) defines a subgroup of breast tumors with aggressive behavior. The addition of HER2-targeted antibodies (i.e., trastuzumab, pertuzumab) to chemotherapy significantly improves relapse-free and overall survival in patients with early-stage and advanced disease. Nonetheless, considerable proportions of patients develop resistance to treatment, highlighting the need for additional and co-adjuvant therapeutic strategies. HER2-specific antibodies can trigger natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity and indirectly enhance the development of tumor-specific T cell immunity; both mechanisms contributing to their antitumor efficacy in preclinical models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29180606/novel-baff-receptor-antibody-to-natively-folded-recombinant-protein-eliminates-drug-resistant-human-b-cell-malignancies-in-vivo
#10
Hong Qin, Guowei Wei, Ippei Sakamaki, Zhenyuan Dong, Wesley A Cheng, D Lynne Smith, Feng Wen, Han Sun, Kunhwa Kim, Soung-Chul Cha, Laura Bover, Sattva S Neelapu, Larry W Kwak
PURPOSE: Monoclonal antibodies (mAbs) such as anti-CD20 rituximab, are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy. EXPERIMENTAL DESIGN: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell-surface immunogen on mouse fibroblast cells...
November 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29162646/nkg2d-dependent-anti-tumor-effects-of-chemotherapy-and-radiotherapy-against-glioblastoma
#11
Tobias Weiss, Hannah Schneider, Manuela Silginer, Alexander Steinle, Martin N Pruschy, Bojan Polic, Michael Weller, Patrick Roth
PURPOSE: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. EXPERIMENTAL DESIGN: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy...
November 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29162391/impact-of-hiv-1-envelope-conformation-on-adcc-responses
#12
REVIEW
Jonathan Richard, Jérémie Prévost, Nirmin Alsahafi, Shilei Ding, Andrés Finzi
HIV-1 envelope glycoproteins (Env) represent the only virus-specific antigen exposed at the surface of infected cells. In its unliganded form, Env from primary viruses samples a 'closed' conformation (State 1), which is preferentially recognized by broadly neutralizing antibodies (bNAbs). CD4 engagement drives Env into an intermediate 'partially open' (State 2) and then into the 'open' CD4-bound conformation (State 3). Emerging evidence suggests a link between Env conformation and Ab-dependent cellular cytotoxicity (ADCC)...
November 18, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29152068/age-associated-and-therapy-induced-alterations-in-the-cellular-microenvironment-of-experimental-gliomas
#13
Hannah Schneider, Birthe Lohmann, Hans-Georg Wirsching, Kathy Hasenbach, Elisabeth J Rushing, Karl Frei, Martin Pruschy, Ghazaleh Tabatabai, Michael Weller
The poor prognosis associated with advanced age in patients with glioblastoma remains poorly understood. Glioblastoma in the elderly has been particularly associated with vascular endothelial growth factor (VEGF)-dependent angiogenesis, and early uncontrolled studies suggested that the anti-angiogenic agent bevacizumab (BEV), an antibody to VEGF, might be preferentially active in this patient population. Accordingly, we explored host age-dependent differences in survival and benefit from radiotherapy (RT) or BEV in syngeneic mouse glioma models...
October 20, 2017: Oncotarget
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
#14
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/29129698/evaluation-of-different-parameters-of-humoral-and-cellular-immune-responses-in-hiv-serodiscordant-heterosexual-couples-humoral-response-potentially-implicated-in-modulating-transmission-rates
#15
María Julia Ruiz, Jimena Salido, Lorena Abusamra, Yanina Ghiglione, Cintia Cevallos, Gabriel Damilano, Ana María Rodriguez, César Trifone, Natalia Laufer, Luis D Giavedoni, Omar Sued, Horacio Salomón, María Magdalena Gherardi, Gabriela Turk
As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC) represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC) activity were assessed in nine HIV-exposed seronegative individuals (ESN) and their corresponding HIV seropositive partners (HIV(+)-P), in eighteen chronically infected HIV subjects (C), nine chronically infected subjects known to be HIV transmitters (CT) and ten healthy HIV(-) donors (HD)...
November 3, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29123953/pd-1-blockade-augments-anti-neuroblastoma-immune-response-induced-by-anti-gd2-antibody-ch14-18-cho
#16
Nikolai Siebert, Maxi Zumpe, Madlen Jüttner, Sascha Troschke-Meurer, Holger N Lode
Immunotherapy with anti-GD2 antibody (Ab) ch14.18/CHO is effective for treatment of high-risk neuroblastoma (NB) patients and is mainly based on GD2-specific Ab-dependent cellular cytotoxicity (ADCC). Strategies to further enhance the efficacy are important and currently explored in prospective clinical trials randomizing ch14.18/CHO ± IL-2. Recently, expression of programmed death 1 (PD-1) inhibitory receptor by effector cells and its ligand (PD-L1) by tumor cells has been shown. Here, we report for the first time effects of PD-1 blockade on ch14...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29113954/an-improved-method-to-quantify-human-nk-cell-mediated-antibody-dependent-cell-mediated-cytotoxicity-adcc-per-igg-fcr-positive-nk-cell-without-purification-of-nk-cells
#17
Alexander P Sung, Jennifer J-J Tang, Michael J Guglielmo, Doug Redelman, Julie Smith-Gagen, Lucinda Bateman, Dorothy Hudig
Natural killer (NK) lymphocyte ADCC supports anti-viral protection and monoclonal antibody (mAb) anti-tumor therapies. To predict in vivo ADCC therapeutic responses of different individuals, measurement of both ADCC cellular lytic capacity and their NK cellular receptor recognition of antibodies on 'target' cells are needed, using clinically available amounts of blood. Twenty ml of blood provides sufficient peripheral blood mononuclear cells (PBMCs) for the new assay for lytic capacity described here and for an antibody EC50 assay for Fc-receptor recognition...
November 4, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29106590/antibody-dependent-cellular-cytotoxicity-adcc-responses-to-seasonal-influenza-vaccination-in-older-adults
#18
Hillary A Vanderven, Sinthujan Jegaskanda, Bruce D Wines, P Mark Hogarth, Sarina Carmuglia, Steven Rockman, Amy W Chung, Stephen J Kent
Background: Older adults are at high-risk of influenza disease, but generally respond poorly to vaccination. Antibody-dependent cellular cytotoxicity (ADCC) may be an important component of protection against influenza infection. An improved understanding of the ADCC response to influenza vaccination in older adults is required. Methods: We studied sera samples from three groups of subjects aged 65 years (n=16-17/group) receiving the 2008/2009 seasonal trivalent influenza vaccine (TIV)...
November 2, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29103968/anti-pd-l1-tgf%C3%AE-r2-m7824-fusion-protein-induces-immunogenic-modulation-of-human-urothelial-carcinoma-cell-lines-rendering-them-more-susceptible-to-immune-mediated-recognition-and-lysis
#19
Italia Grenga, Renee N Donahue, Morgan L Gargulak, Lauren M Lepone, Mario Roselli, Marijo Bilusic, Jeffrey Schlom
BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis...
November 2, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29101107/cytokines-in-cancer-immunotherapy
#20
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
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