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https://www.readbyqxmd.com/read/29748553/anticancer-activity-and-antibody-dependent-cell-mediated-cytotoxicity-of-novel-anti-nucleolin-antibodies
#1
Sofia Romano, Vera Moura, Sérgio Simões, João Nuno Moreira, João Gonçalves
Nucleolin arises as a relevant target for cancer therapy, as it is overexpressed at the surface of cancer and angiogenic endothelial cells thus enabling a dual cellular targeting strategy. Immunotherapeutic strategies, albeit of proven therapeutic relevance, have been scarcely explored against this target. Therefore, this work aimed at engineering an anti-nucleolin VHH-based antibody capable of triggering anticancer immune responses. Herein, anti-nucleolin VHHs have been generated upon grafting F3 peptide-derived nucleolin-binding sequences onto a VHH CDR1 or CDR3...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29748373/slan-monocytes-and-macrophages-mediate-cd20-dependent-b-cell-lymphoma-elimination-via-adcc-and-adcp
#2
William Vermi, Alessandra Micheletti, Giulia Finotti, Cristina Tecchio, Federica Calzetti, Sara Costa, Mattia Bugatti, Stefano Calza, Claudio Agostinelli, Stefano Pileri, Piera Balzarini, Alessandra Tucci, Giuseppe Rossi, Lara Furlani, Giuseppe Todeschini, Alberto Zamò, Fabio Facchetti, Luisa Lorenzi, Silvia Lonardi, Marco A Cassatella
Terminal tissue differentiation and function of slan+ monocytes in cancer is largely unexplored. Our recent studies demonstrated that slan+ monocytes differentiate into a distinct subset of dendritic cells (DC) in human tonsils and that slan+ cells colonize metastatic carcinoma-draining lymph nodes. Herein, we report by retrospective analysis of multi-institutional cohorts that slan+ cells infiltrate various types of non-Hodgkin lymphomas (NHL), particularly the diffuse large B-cell lymphoma (DLBCL) group, including the most aggressive, nodal and extra-nodal, forms...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29739434/gastric-cancer-vaccines-synthesized-using-a-tlr7-agonist-and-their-synergistic-antitumor-effects-with-5-fluorouracil
#3
Xiaodong Wang, Yu Liu, Yuwen Diao, Ningning Gao, Yanyan Wan, Jingjing Zhong, Huali Zheng, Zhulin Wang, Guangyi Jin
BACKGROUND: Vaccines play increasingly important roles in cancer treatment due to their advantages of effective targeting and few side effects. Our laboratory has attempted to construct vaccines by conjugating TLR7 agonists with tumor-associated antigens. Furthermore, immunochemotherapy has recently become an appealing approach to cancer therapy. 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent, can reportedly potently and selectively kill tumor-associated MDSCs in vivo. METHODS: Gastric cancer vaccines were synthesized by the covalent attachment of our TLR7 agonist with the gastric cancer antigen MG7-Ag tetra-epitope, leading to T7 - ML (linear tetra-epitope) and T7 - MB (branched tetra-epitope)...
May 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29733746/the-less-is-more-in-therapeutic-antibodies-afucosylated-anti-cancer-antibodies-with-enhanced-antibody-dependent-cellular-cytotoxicity
#4
Natasha A Pereira, Kah Fai Chan, Pao Chun Lin, Zhiwei Song
Therapeutic monoclonal antibodies are the fastest growing class of biological therapeutics for the treatment of various cancers and inflammatory disorders. In cancer immunotherapy, some IgG1 antibodies rely on the Fc-mediated immune effector function, antibody-dependent cellular cytotoxicity (ADCC), as the major mode of action to deplete tumor cells. It is well-known that this effector function is modulated by the N-linked glycosylation in the Fc region of the antibody. In particular, absence of core fucose on the Fc N-glycan has been shown to increase IgG1 Fc binding affinity to the FcγRIIIa present on immune effector cells such as natural killer cells and lead to enhanced ADCC activity...
May 7, 2018: MAbs
https://www.readbyqxmd.com/read/29702148/immunomodulatory-effects-of-cd38-targeting-antibodies
#5
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/29669829/incomplete-downregulation-of-cd4-expression-affects-hiv-1-env-conformation-and-adcc-responses
#6
Jérémie Prévost, Jonathan Richard, Halima Medjahed, Audrey Alexander, Jennifer Jones, John C Kappes, Christina Ochsenbauer, Andrés Finzi
HIV-1 infected cells expressing envelope glycoproteins (Env) in the CD4-bound conformation on their surface are targeted by antibody-dependent cellular cytotoxicity (ADCC) mediated by CD4-induced (CD4i) antibodies and HIV+ sera. By downregulating the surface expression of CD4, Nef prevents Env-CD4 interaction thus protecting HIV-1-infected cells from ADCC. HIV-1 infectious molecular clones (IMC) are widely used to measure ADCC. In order to facilitate the identification of infected cells and high-throughput ADCC analysis, reporter genes (e...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29651286/iga-targeting-human-immunodeficiency-virus-1-envelope-gp41-triggers-antibody-dependent-cellular-cytotoxicity-cross-clade-and-cooperates-with-gp41-specific-igg-to-increase-cell-lysis
#7
Maxence Duchemin, Marwa Khamassi, Lin Xu, Daniela Tudor, Morgane Bomsel
The protective efficacy of human immunodeficiency virus-1 (HIV-1) antibodies (Abs) remains mostly correlated with their in vitro neutralizing activity engaging their Fab region. However, anti-HIV-1 Abs also mediate a broad array of Fc-mediated effector functions including Ab-dependent cellular cytotoxicity (ADCC), which depend primarily on the Ab isotype. While ADCC is commonly associated with HIV-1 gp120 envelope-specific IgGs, whether IgAs, especially those targeting the HIV-1 gp41 envelope, also mediate ADCC remains elusive...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29600574/quantitative-assessment-of-mab-fc-glycosylation-of-cqa-importance-by-capillary-electrophoresis
#8
Marton Szigeti, Jeff Chapman, Beata Borza, Andras Guttman
The attached carbohydrates at the highly conserved asparagine-linked glycosylation site in the CH 2 domain of the fragment crystallizable (Fc) region of monoclonal antibody therapeutics can play an essential role in their mechanism of action, including ADCC, CDC, anti-inflammatory functions, and serum half-life. Thus, this particular glycosylation represents one of the important critical quality attributes (CQA) of therapeutic monoclonal antibodies, which should be closely monitored and controlled during all stages of biopharmaceutical manufacturing...
March 30, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29572470/transcriptomic-signatures-of-nk-cells-suggest-impaired-responsiveness-in-hiv-1-infection-and-increased-activity-post-vaccination
#9
Margaret C Costanzo, Dohoon Kim, Matthew Creegan, Kerri G Lal, Julie A Ake, Jeffrey R Currier, Hendrik Streeck, Merlin L Robb, Nelson L Michael, Diane L Bolton, Nicholas J Steers, Michael A Eller
Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK cells responding to models of direct cell recognition, ADCC, and cytokine activation have unique transcriptional fingerprints. Compared with healthy volunteers, individuals with chronic HIV-1 infection have higher expression of genes commonly associated with activation, and lower expression of genes associated with direct cell recognition and cytokine stimulation in their NK cells...
March 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29568351/targeting-of-embryonic-annexin-a2-expressed-on-ovarian-and-breast-cancer-by-the-novel-monoclonal-antibody-2448
#10
Simeon Cua, Heng Liang Tan, Wey Jia Fong, Angela Chin, Ally Lau, Vanessa Ding, Zhiwei Song, Yuansheng Yang, Andre Choo
Monoclonal antibodies (mAbs) play an increasingly important role in cancer therapy. To address the wide heterogeneity of the disease, the identification of novel antigen targets and the development of mAbs against them are needed. Our lab previously generated a panel of mAbs against human embryonic stem cells (hESC) using a whole cell immunization approach in mice. These mAbs can potentially target oncofetal antigens and be repurposed for antibody or antibody drug conjugate (ADC) therapy. From this panel, the novel IgG1 2448 was found to bind surface antigens on hESC and multiple cancer cell lines...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29554481/the-transgenic-chicken-derived-anti-cd20-monoclonal-antibodies-exhibits-greater-anti-cancer-therapeutic-potential-with-enhanced-fc-effector-functions
#11
Young Min Kim, Jin Se Park, Sang Kyung Kim, Kyung Min Jung, Young Sun Hwang, Mookyoung Han, Hong Jo Lee, Hee Won Seo, Jeong-Yong Suh, Beom Ku Han, Jae Yong Han
Modern genetic techniques, enable the use of animal bioreactor systems for the production and functional enhancement of anti-cancer antibodies. Chicken is the most efficient animal bioreactor for the production of anti-cancer antibodies because of its relatively short generation time, plentiful reproductive capacity, and daily deposition in the egg white. Although several studies have focused on the production of anti-cancer antibodies in egg white, in-depth studies of the biological activity and physiological characteristics of transgenic chicken-derived anti-cancer antibodies have not been fully carried out...
June 2018: Biomaterials
https://www.readbyqxmd.com/read/29536036/human-cytomegalovirus-infection-increases-both-antibody-and-non-antibody-dependent-cellular-reactivity-by-natural-killer-cells
#12
Clive M Michelo, Bram van Cranenbroek, Peran Touw, Frans H J Claas, Arnold van der Meer, Irma Joosten
Background: Antibody-mediated rejection in solid organ transplantation is an important immunological barrier to successful long-term graft survival. Next to complement activation, natural killer (NK) cells have been implicated in the process. Human cytomegalovirus (CMV), independently associated with decreased graft survival, has a strong imprint on the immune response. Here, we assessed the effect of CMV status on alloreactive NK cell reactivity. Methods: We compared antibody-mediated NK cell cytolytic activity (CD107a expression) and IFNγ production between healthy CMV-seropositive (n = 8) and CMV-seronegative (n = 11) individuals, in cocultures of NK cells with anti-HLA class I or rituximab (control) antibody-coated Raji cells...
December 2017: Transplantation Direct
https://www.readbyqxmd.com/read/29515764/polo-like-kinase-inhibitor-volasertib-marginally-enhances-the-efficacy-of-the-novel-fc-engineered-anti-cd33-antibody-bi-836858-in-acute-myeloid-leukemia
#13
Bhavani Gopalakrishnan, Carolyn Cheney, Rajeswaran Mani, Xiaokui Mo, Donna Bucci, Alison Walker, Rebecca Klisovic, Bhavana Bhatnagar, Katherine Walsh, Bjoern Rueter, Irene C Waizenegger, Karl-Heinz Heider, William Blum, Sumithira Vasu, Natarajan Muthusamy
Acute myeloid leukemia (AML) is the second most common type of leukemia in adults. Incidence of AML increases with age with a peak incidence at 67 years. Patients older than 60 years have an unfavorable prognosis due to resistance to conventional chemotherapy. Volasertib (BI 6727) is a cell-cycle regulator targeting polo-like kinase which has been evaluated in clinical trials in AML. We evaluated effects of volasertib in primary patient samples and NK cells. At equivalent doses, volasertib is cytotoxic to AML blasts but largely spares healthy NK cells...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29478343/pd-l1-inhibition-with-avelumab-for-metastatic-merkel-cell-carcinoma
#14
REVIEW
Maria Rita Gaiser, Michelle Bongiorno, Isaac Brownell
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that lacks durable responses to traditional chemotherapy. Areas covered: After MCC was shown to be an immunogenic tumor, small trials revealed high objective response rates to PD-1/PD-L1 checkpoint inhibitors. The JAVELIN Merkel 200 (NCT02155647) trial tested the use of avelumab, a human IgG1 monoclonal antibody against PD-L1, in metastatic MCC. Avelumab recently became the first approved drug for metastatic MCC. Expert commentary: By conducting broad phase I studies assessing the safety of avelumab and a small phase II study demonstrating efficacy in this rare orphan tumor type, avelumab gained accelerated approval for the treatment of metastatic MCC...
April 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29400603/a-novel-bicistronic-gene-design-couples-stable-cell-line-selection-with-a-fucose-switch-in-a-designer-cho-host-to-produce-native-and-afucosylated-glycoform-antibodies
#15
Gargi Roy, Tom Martin, Arnita Barnes, Jihong Wang, Rod Brian Jimenez, Megan Rice, Lina Li, Hui Feng, Shu Zhang, Raghothama Chaerkady, Herren Wu, Marcello Marelli, Diane Hatton, Jie Zhu, Michael A Bowen
The conserved glycosylation site Asn297 of a monoclonal antibody (mAb) can be decorated with a variety of sugars that can alter mAb pharmacokinetics and recruitment of effector proteins. Antibodies lacking the core fucose at Asn297 (afucosylated mAbs) show enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and increased efficacy. Here, we describe the development of a robust platform for the manufacture of afucosylated therapeutic mAbs by engineering a Chinese hamster ovary (CHO) host cell line to co-express a mAb with GDP-6-deoxy-D-lyxo-4-hexulose reductase (RMD), a prokaryotic enzyme that deflects an intermediate in the de novo synthesis of fucose to a dead-end product, resulting in the production of afucosylated mAb (GlymaxX™ Technology, ProBioGen)...
April 2018: MAbs
https://www.readbyqxmd.com/read/29371955/a-comparative-global-phosphoproteomics-analysis-of-obinutuzumab-ga101-versus-rituximab-rtx-against-rtx-sensitive-and-resistant-burkitt-lymphoma-bl-demonstrates-differential-phosphorylation-of-signaling-pathway-proteins-after-treatment
#16
Aradhana Awasthi, Delphine C M Rolland, Janet Ayello, Carmella van de Ven, Venkatesha Basrur, Kevin Conlon, Damian Fermin, Matthew J Barth, Christian Klein, Kojo S J Elenitoba-Johnson, Megan S Lim, Mitchell S Cairo
We recently demonstrated that obinutuzumab (GA101), a novel glycoengineered type II CD20 Ab compared to rituximab (RTX) mediates significantly enhanced antibody-dependent cell cytotoxicity (ADCC) in vitro and increased overall survival in a Burkitt lymphoma (BL) xenograft non-obese diabetic severe combined immunodeficiency gamma (NSG) model. In this study we compared the phosphoproteomic changes by pathway analysis following obinutuzumab vs RTX against RTX-sensitive (Raji) and -resistant BL (Raji4RH). Phosphoproteomic analyses were performed by mass-spectrometry (MS)-based label-free quantitative phosphoproteomic profiling...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273355/what-is-the-most-important-for-elite-control-genetic-background-of-patient-genetic-background-of-partner-both-or-neither-description-of-complete-natural-history-within-a-couple-of-msm
#17
M Bendenoun, A Samri, V Avettand-Fènoël, S Cardinaud, B Descours, G Carcelain, M-C Mazeron, J-F Bergmann, A Urrutia, A Moris, C Rouzioux, F Simon, P Andre, M Pocard, X Dray, T Mourez, V Vieillard, B Autran, F Barin, P Sellier
BACKGROUND: We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background. METHODS: HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined. FINDINGS: Two HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay...
January 2018: EBioMedicine
https://www.readbyqxmd.com/read/29247515/intrahepatic-and-peripheral-blood-phenotypes-of-natural-killer-and-t-cells-differential-surface-expression-of-killer-cell-immunoglobulin-like-receptors
#18
Ariel Podhorzer, Andrés Machicote, Santiago Belén, Leandro Lauferman, Oscar Imventarza, Silvina Montal, Sebastián Marciano, Omar Galdame, Luis G Podesta, Leonardo Fainboim
Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood natural killer (NK), natural killer T (NKT) and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activation marker NKp44...
December 16, 2017: Immunology
https://www.readbyqxmd.com/read/29245952/the-humanized-anti-human-amhrii-mab-3c23k-exerts-an-anti-tumor-activity-against-human-ovarian-cancer-through-tumor-associated-macrophages
#19
Houcine Bougherara, Fariba Némati, André Nicolas, Gérald Massonnet, Martine Pugnière, Charlotte Ngô, Marie-Aude Le Frère-Belda, Alexandra Leary, Jérôme Alexandre, Didier Meseure, Jean-Marc Barret, Isabelle Navarro-Teulon, André Pèlegrin, Sergio Roman-Roman, Jean-François Prost, Emmanuel Donnadieu, Didier Decaudin
Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, such as human ovarian cancers (OCs). On this basis, a humanized glyco-engineered monoclonal antibody (3C23K) has been developed. The aim of this study was therefore to experimentally confirm the therapeutic potential of 3C23K in human OCs. We first determined by immunofluorescence, immunohistochemistry and cytofluorometry analyses the expression of AMHRII in patient's tumors and found that a majority (60 to 80% depending on the detection technique) of OCs were positive for this marker...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222435/long-term-maintenance-of-peripheral-blood-derived-human-nk-cells-in-a-novel-human-il-15-transgenic-nog-mouse
#20
Ikumi Katano, Chiyoko Nishime, Ryoji Ito, Tsutomu Kamisako, Takuma Mizusawa, Yuyo Ka, Tomoyuki Ogura, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
We generated a novel mouse strain expressing transgenic human interleukin-15 (IL-15) using the severe immunodeficient NOD/Shi-scid-IL-2Rγnull (NOG) mouse genetic background (NOG-IL-15 Tg). Human natural killer (NK) cells, purified from the peripheral blood (hu-PB-NK) of normal healthy donors, proliferated when transferred into NOG-IL-15 Tg mice. In addition, the cell number increased, and the hu-PB-NK cells persisted for 3 months without signs of xenogeneic graft versus host diseases (xGVHD). These in vivo-expanded hu-PB-NK cells maintained the original expression patterns of various surface antigens, including NK receptors and killer cell immunoglobulin-like receptor (KIR) molecules...
December 8, 2017: Scientific Reports
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