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https://www.readbyqxmd.com/read/29438058/assessment-of-antibody-dependent-cellular-cytotoxicity-by-flow-cytometry
#1
Thomas D Duensing, Susan R Watson
A useful feature of therapeutic antibodies is the ability to kill the cells to which they bind. Antibodies are capable of mediating cell killing in a variety of ways. Apoptosis, complement-mediated mechanisms, and antibody-dependent cellular cytotoxicity (ADCC) are all effects that can be assayed to characterize lead antibody candidates. Extensive, multidose characterizations of a series of candidates can be performed in a short amount of time using assays developed for high-throughput flow cytometry systems...
February 1, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29434980/augmentation-of-antibody-dependent-cellular-cytotoxicity-with-defucosylated-monoclonal-antibodies-in-patients-with-gi-tract-cancer
#2
Takahiro Nakajima, Hirokazu Okayama, Mai Ashizawa, Masaru Noda, Keita Aoto, Motonobu Saito, Tomoyuki Monma, Shinji Ohki, Masahiko Shibata, Seiichi Takenoshita, Koji Kono
Enhancement of antibody-dependent cellular cytotoxicity (ADCC) with some modalities may be a promising approach to enhance the efficacy of therapeutic monoclonal antibodies (mAbs). It has previously been demonstrated that the removal of fucose from antibody oligosaccharides (defucosylation) leads to augmentation of ADCC activity. To establish clinically relevant evidence of this procedure, the present study evaluated trastuzumab- and cetuximab-mediated ADCC by comparing defucosylated mAbs with conventional mAbs using peripheral blood mononuclear cells (PBMCs)...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29426894/site-specific-n-glycosylation-analysis-of-soluble-fc%C3%AE-receptor-iiib-in-human-serum
#3
Hirokazu Yagi, Daisuke Takakura, Lubka T Roumenina, Wolf Herman Fridman, Catherine Sautès-Fridman, Nana Kawasaki, Koichi Kato
Fc-receptors for immunoglobulin G (FcγRs) mediate a variety of effector and regulatory mechanisms in the immune system. N-glycosylation of FcγRs critically affects their functions which is well exemplified by antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis mediated by homologous FcγRIIIa and FcγRIIIb, respectively. Although several reports describe N-glycosylation profiles of recombinant FcγRIII glycoproteins, much remains unknown regarding their native glycoforms. Here we performed site-specific N-glycosylation profiling of a soluble form of FcγRIIIb purified from human serum based on mass spectrometric analysis...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29416099/generation-and-characterization-of-a-igg-monoclonal-antibody-specific-for-gm3-neugc-ganglioside-by-immunizing-%C3%AE-3gn-t5-knockout-mice
#4
Dongwei He, Xiaoyan Fan, Boyi Liu, Yiqing Tian, Xiangmei Zhang, Lin Kang, Yan Tai, Shuzhen Liu, Qian Wang, Qingxia Li, Jianhui Cai
A murine monoclonal antibody (MAb-1) specific for GM3 has been generated by immunizing β3Gn-T5 knockout mice with purified GM3 ganglioside. The binding specificity of MAb-1 (IgG3 subclass) was established by an enzyme-linked immunosorbent assay (ELISA) and FACS and the antibody showed high binding specificity with GM3. Cell viability assay showed that MAb-1 significantly suppressed cell growth. Immunohistochemistry analysis revealed that MAb-1 was strongly expressed in human ovarian cancer tissues, whereas it was hardly expressed in normal tissues...
February 7, 2018: Scientific Reports
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
#5
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)...
February 5, 2018: MAbs
https://www.readbyqxmd.com/read/29388200/phase-i-clinical-trial-of-adoptive-transfer-of-expanded-natural-killer-cells-in-combination-with-igg1-antibody-in-patients-with-gastric-or-colorectal-cancer
#6
Takeshi Ishikawa, Tetsuya Okayama, Naoyuki Sakamoto, Mitsuko Ideno, Kaname Oka, Tatsuji Enoki, Junichi Mineno, Naohisa Yoshida, Kazuhiro Katada, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Hideyuki Konishi, Satoshi Kokura, Kazuko Uno, Yuji Naito, Yoshito Itoh
Natural killer (NK) cells exhibit strong cytotoxic activity against tumor cells without prior sensitization, and have the potential to exert antibody-dependent cellular cytotoxicity (ADCC). In this clinical trial, we examined the safety and efficacy of the use of NK cells, generated using a novel expansion system, in combination with IgG1 antibodies for the treatment of advanced gastric or colorectal cancers. Treatment consisted of trastuzumab- or cetuximab-based chemotherapy, plus adoptive NK cell therapy...
January 31, 2018: International Journal of Cancer. Journal International du Cancer
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
#7
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/29364738/mutation-analysis-of-families-with-autosomal-dominant-congenital-cataract-a-recurrent-mutation-in-the-cryba1-a3-gene-causing-congenital-nuclear-cataract
#8
Kai Jie Wang, Xu Zha, Dou Dou Chen, Si Quan Zhu
PURPOSE: To identify the CRYBA1/A3 mutation spectrum and analyze the genotype-phenotype correlations in Chinese families with congenital cataract. METHODS: Family history and clinical data of 47 unrelated families with autosomal dominant congenital cataract (ADCC) were recorded. CRYBA1/A3 gene sequencing was applied to identify the causative mutation. Haplotypes were constructed using closely linked microsatellite markers and intragenic single-nucleotide polymorphisms (SNPs) to compare the affected haplotype in three families...
January 24, 2018: Current Eye Research
https://www.readbyqxmd.com/read/29363526/nitric-oxide-production-by-myeloid-derived-suppressor-cells-plays-a-role-in-impairing-fc-receptor-mediated-natural-killer-cell-function
#9
Andrew Stiff, Prashant Trikha, Bethany L Mundy-Bosse, Elizabeth L McMichael, Thomas A Mace, Brooke Benner, Kari Kendra, Amanda Campbell, Shalini Gautam, David Abood, Ian Landi, Vincent Hsu, Megan C Duggan, Robert Wesolowski, Matthew Old, John H Howard, Lianbo Yu, Nancy Stasik, Thomas Olencki, Natarajan Muthusamy, Susheela Tridandapani, John C Byrd, Michael A Caligiuri, William E Carson
PURPOSE: Monoclonal antibodies (mAb) are used to treat solid and hematological malignancies, and work in part through Fc receptors (FcR) on natural killer cells (NK). However, FcR mediated functions of NK cells from cancer patients are significantly impaired. Identifying the mechanisms of this dysfunction and impaired response to mAb therapy could lead to combination therapies and enhance mAb therapy.  Experimental Design: Co-cultures of autologous NK cells and MDSC from cancer patients were used to study the effect of MDSC on NK cell FcR mediated functions including antibody dependent cellular cytotoxicity, cytokine production, and signal transduction in vitro...
January 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29362133/prediction-of-distant-metastasis-and-survival-in-adenoid-cystic-carcinoma-using-quantitative-18f-fdg-pet-ct-measurements
#10
Won Sub Lim, Jungsu S Oh, Jong-Lyel Roh, Jae Seung Kim, Soo-Jong Kim, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim
OBJECTIVES: Adenoid cystic carcinoma (AdCC) in the salivary gland shows a high rate of distant metastasis, which is related to the resulting poor prognosis. We therefore examined the role of pretreatment 18F-FDG PET/CT for prediction of distant metastasis, recurrence/progression, and survival in AdCC. METHODS: This study included 52 patients who underwent pretreatment 18F-FDG PET/CT scanning and subsequent treatments for AdCC. Maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT...
February 2018: Oral Oncology
https://www.readbyqxmd.com/read/29350566/abp-501-for-the-treatment-of-rheumatoid-arthritis
#11
Eleftherios Pelechas, Paraskevi V Voulgari, Alexandros A Drosos
Rheumatoid arthritis (RA) is an autoimmune disease, which has a negative impact on the ability to perform activities daily. Tumour necrosis factor α (TNF) is a cytokine with diverse cellular effects, and a key regulator of the inflammatory response. ABP 501 is a biosimilar to adalimumab, a TNF inhibitor. Areas covered: In this review, we examined ABP 501, as a biosimilar candidate to adalimumab in the treatment of RA focusing on the available data. Current data indicate that ABP 501 is a highly similar alternative to adalimumab in terms of safety, efficacy, tolerability and immunogenicity...
January 19, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29327110/the-role-of-interleukin-2-all-trans-retinoic-acid-and-natural-killer-cells-surveillance-mechanisms-in-anti-gd2-antibody-therapy-in-neuroblastoma
#12
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29323175/functional-antibody-response-against-v1v2-and-v3-of-hiv-gp120-in-the-vax003-and-vax004-vaccine-trials
#13
Preetha Balasubramanian, Constance Williams, Mariya B Shapiro, Faruk Sinangil, Keith Higgins, Arthur Nádas, Maxim Totrov, Xiang-Peng Kong, Andrew J Fiore-Gartland, Nancy L Haigwood, Susan Zolla-Pazner, Catarina E Hioe
Immunization with HIV AIDSVAX gp120 vaccines in the phase III VAX003 and VAX004 trials did not confer protection. To understand the shortcomings in antibody (Ab) responses induced by these vaccines, we evaluated the kinetics of Ab responses to the V1V2 and V3 regions of gp120 and the induction of Ab-mediated antiviral functions during the course of 7 vaccinations over a 30.5-month period. Plasma samples from VAX003 and VAX004 vaccinees and placebo recipients were measured for ELISA-binding Abs and for virus neutralization, Ab-dependent cellular phagocytosis (ADCP), and Ab-dependent cellular cytotoxicity (ADCC)...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29305595/frequency-analysis-of-the-g-7081t-g-a-and-g-10872t-g-polymorphisms-in-the-fcgr3a-gene-cd16a-using-nested-pcr-and-their-functional-specific-effects
#14
Camilo Andrés Pérez-Romero, Isaura Pilar Sánchez, Laura Naranjo-Piedrahita, Julio Cesar Orrego-Arango, Carlos Enrique Muskus-López, Winston Rojas-Montoya, Jose Luis Franco Restrepo, Claudia Milena Trujillo-Vargas
Polymorphic variants p.66L>R/H (g.7081T>G/A; rs10127939) and p.176F>V (g.10872T>G; rs396991) in FCGR3A (CD16A) have been associated with defects in cytotoxic function of natural killer (NK) cells in humans. Genotyping of these variants in genomic DNA has been ambiguous because of high degree of homology between FCGR3A and FCGR3B. We designed a strategy to genotype these polymorphisms and to evaluate their effects on NK cells' cytotoxic activity. One hundred and fifteen individuals from different geographical regions of Colombia were included...
January 5, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29296857/effects-of-daratumumab-on-natural-killer-cells-and-impact-on-clinical-outcomes-in-relapsed-or-refractory-multiple-myeloma
#15
Tineke Casneuf, Xu Steven Xu, Homer C Adams, Amy E Axel, Christopher Chiu, Imran Khan, Tahamtan Ahmadi, Xiaoyu Yan, Sagar Lonial, Torben Plesner, Henk M Lokhorst, Niels W C J van de Donk, Pamela L Clemens, A Kate Sasser
Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy and safety, were assessed...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29277772/deregulation-of-nicotinamide-n-methyltransferase-and-gap-junction-protein-alpha-1-causes-metastasis-in-adenoid-cystic-carcinoma
#16
Kana Ishibashi, Kotaro Ishii, Goro Sugiyama, Tomoki Sumida, Tsuyoshi Sugiura, Y U Kamata, Katsuhiro Seki, Takahiro Fujinaga, Wataru Kumamaru, Yosuke Kobayashi, Naomi Hiyake, Hiroyuki Nakano, Tomohiro Yamada, Yoshihide Mori
BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a malignant tumor that occurs in the salivary glands and frequently metastasizes. The aim of this study was to identify factors mediating AdCC metastasis. MATERIALS AND METHODS: We established three AdCC cell lines by orthotropic transplantation and in vivo selection: parental, highly metastatic (ACCS-M-GFP), and lymph node metastatic (ACCS-LN-GFP) cells. RESULTS: We examined the three cell lines...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29275362/regulation-of-%C3%AE-catenin-phosphorylation-by-pr55%C3%AE-in-adenoid-cystic-carcinoma
#17
Kana Ishibashi, Kotaro Ishii, Goro Sugiyama, Y U Kamata, Azusa Suzuki, Wataru Kumamaru, Yukiko Ohyama, Hiroyuki Nakano, Tamotsu Kiyoshima, Tomoki Sumida, Tomohiro Yamada, Yoshihide Mori
BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. β-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including β-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M)...
January 2018: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29273432/the-alpha-helix-1-from-the-first-conserved-region-of-hiv1-gp120-is-reconstructed-in-the-short-nq21-peptide
#18
Vladislav Victorovich Khrustalev, Tatyana Aleksandrovna Khrustaleva, Ekaterina Yurievna Kahanouskaya, Yulia Anatolyevna Rudnichenko, Hanna Vitalyevna Bandarenka, Alexander Migranovich Arutyunyan, Kseniya Victorovna Girel, Nadia Vladimirovna Khinevich, Alexander Leonidovich Ksenofontov, Larisa Valentinovna Kordyukova
Investigations of short peptides that can be used in the next phase of synthetic HIV1 vaccine development are an urgent goal, as well as investigations of peptides that can be used in immunological tests with the aim to check the titer of antibodies against the alpha helix 1 from the first conserved region of HIV1 gp120 that are known to cause antibody-dependent cellular cytotoxicity (ADCC). The aim of this work was to study the structure of the NQ21 peptide corresponding to the less mutable part of the first conserved region of HIV1 gp120 (residues 94-114)...
December 19, 2017: Archives of Biochemistry and Biophysics
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
#19
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...
December 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29259299/two-novel-mutations-identified-in-adcc-families-impair-crystallin-protein-distribution-and-induce-apoptosis-in-human-lens-epithelial-cells
#20
Li Li, Da-Bei Fan, Ya-Ting Zhao, Yun Li, De-Qian Kong, Fang-Fei Cai, Guang-Ying Zheng
Congenital cataract (CC) is a clinical and genetically heterogeneous eye disease that primarily causes lens disorder and even amblyopic blindness in children. As the mechanism underlying CC is genetically inherited, identification of CC-associated gene mutations and their role in protein distribution are topics of both pharmacological and biological research. Through physical and ophthalmic examinations, two Chinese pedigrees with autosomal dominant congenital cataract (ADCC) were recruited for this study. Mutation analyses of CC candidate genes by next-generation sequencing (NGS) and Sanger sequencing revealed a novel missense mutation in CRYBB2 (p...
December 19, 2017: Scientific Reports
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