10,892 results match your criteria antibody-dependent cellular

3D tumor spheroid microarray for high-throughput, high-content natural killer cell-mediated cytotoxicity.

Commun Biol 2021 Jul 21;4(1):893. Epub 2021 Jul 21.

Department of Chemical and Biological Engineering, and Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.

Immunotherapy has emerged as a promising approach to treating several forms of cancer. Use of immune cells, such as natural killer (NK) cells, along with small molecule drugs and antibodies through antibody dependent cell-mediated cytotoxicity (ADCC) has been investigated as a potential combination therapy for some difficult to treat solid tumors. Nevertheless, there remains a need to develop tools that support co-culture of target cancer cells and effector immune cells in a contextually relevant three-dimensional (3D) environment to provide a rapid means to screen for and optimize ADCC-drug combinations. Read More

View Article and Full-Text PDF

CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1.

Sci Rep 2021 Jul 21;11(1):14849. Epub 2021 Jul 21.

Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach, Germany.

More than 70% of colorectal, prostate, ovarian, pancreatic and breast cancer specimens show expression of CD276 (B7-H3), a potential immune checkpoint family member. Several studies have shown that high CD276 expression in cancer cells correlates with a poor clinical prognosis. This has been associated with the presence of lower tumor infiltrating leukocytes. Read More

View Article and Full-Text PDF

Novel mechanisms of action contributing to Benralizumab's potent anti-eosinophilic activity.

Eur Respir J 2021 Jul 21. Epub 2021 Jul 21.

Bioscience COPD/IPF, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA

Benralizumab is a humanised, anti-IL-5Rα monoclonal antibody with anti-eosinophilic activity. Lack of fucose (afucosylation) increases its affinity to CD16a and significantly enhances antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells. Although benralizumab proved clinically efficacious in clinical trials for patients with severe asthma and hypereosinophilic syndrome, in-depth characterisation of its anti-eosinophilic mechanisms of action remain elusive. Read More

View Article and Full-Text PDF

Physicochemical and functional characterization of trastuzumab-dkst, a trastuzumab biosimilar.

Future Med Chem 2021 Jul 22. Epub 2021 Jul 22.

Viatris Inc, Plot No 564/A/22, Road No 92, Jubilee Hills, Hyderabad, 500034, India.

Preclinical comparative similarity studies of trastuzumab-dkst, a Herceptin biosimilar, are reported. Primary sequence and higher-order structure and pharmacological mechanisms of action were compared using multiple techniques. Pharmacokinetics and repeat-dose toxicity were assessed in cynomolgus monkeys. Read More

View Article and Full-Text PDF

The use of tafasitamab in diffuse large B-cell lymphoma.

Ther Adv Hematol 2021 6;12:20406207211027458. Epub 2021 Jul 6.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Patients who relapse or are refractory after first-line therapy for diffuse large B-cell lymphoma (DLBCL) frequently have poor prognoses, especially when they are not candidates for autologous stem cell transplant (ASCT). Tafasitamab is a humanized monoclonal anti-CD19 antibody that has recently been approved by the FDA in combination with lenalidomide for the treatment of relapsed/refractory (R/R) DLBCL in patients who are not eligible for ASCT. Tafasitamab has an Fc region which has been modified to have an increased affinity for Fcγ receptors, to potentiate antibody-dependent cellular cytotoxicity and antibody-dependent cell-mediated phagocytosis. Read More

View Article and Full-Text PDF

Molecular Dynamics Simulations Reveal Interactions of an IgG1 Antibody With Selected Fc Receptors.

Front Chem 2021 2;9:705931. Epub 2021 Jul 2.

Theory Department, National Institute of Chemistry, Ljubljana, Slovenia.

In a survey of novel interactions between an IgG1 antibody and different Fcγ receptors (FcγR), molecular dynamics simulations were performed of interactions of monoclonal antibody involved complexes with FcγRs. Free energy simulations were also performed of isolated wild-type and substituted Fc regions bound to FcγRs with the aim of assessing their relative binding affinities. Two different free energy calculation methods, Molecular Mechanical/Generalized Born Molecular Volume (MM/GBMV) and Bennett Acceptance Ratio (BAR), were used to evaluate the known effector substitution G236A that is known to selectively increase antibody dependent cellular phagocytosis. Read More

View Article and Full-Text PDF

Innovative therapeutic strategy for B-cell malignancies that combines obinutuzumab and cytokine-induced killer cells.

J Immunother Cancer 2021 Jul;9(7)

Department of Surgery, Oncology and Gastroenterology, Immunology and Oncology Section, University of Padua, Padova, Italy

Background: Patients affected by aggressive B-cell malignancies who are resistant to primary or salvage chemoimmunotherapy have an extremely poor prognosis and limited therapeutic options. Promising therapeutic success has been achieved with the infusion of CD19 chimeric antigen receptor-T cells, but several limits still restrain the administration to a limited proportion of patients. This unmet clinical need might be fulfilled by an adoptive immunotherapy approach that combines cytokine-induced killer (CIK) cells and monoclonal antibodies (mAb) to the CD20 antigen. Read More

View Article and Full-Text PDF

Individualized genetic makeup that controls natural killer cell function influences the efficacy of isatuximab immunotherapy in patients with multiple myeloma.

J Immunother Cancer 2021 Jul;9(7)

Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, California, USA

Background: Phase IIb clinical trial with isatuximab (Isa)-lenalidomide (Len)-dexamethasone (Dex) showed an improved progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (RRMM), but the efficacy varied by patient. Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells plays a crucial role in arbitrating antitumor activities of therapeutic-antibodies. We tested if patient-specific genetic makeup known to set NK cell functional threshold influence response to Isa-Len-Dex therapy. Read More

View Article and Full-Text PDF

Physicochemical and biological similarity assessment of LBAL, a biosimilar to adalimumab reference product (Humira®).

Anim Cells Syst (Seoul) 2021 23;25(3):182-194. Epub 2021 Jun 23.

Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan.

LBAL was developed as an adalimumab (Humira®) biosimilar using Chinese hamster ovary cell lines. Comparable quality, safety, and efficacy between a biosimilar and its reference product should be ensured for regulatory approval. Here, we present the results of a comprehensive physicochemical and biological characterization between LBAL and Humira®. Read More

View Article and Full-Text PDF

Factor VIII-Fc Activates Natural Killer Cells Fc-Mediated Interactions With CD16.

Front Immunol 2021 28;12:692157. Epub 2021 Jun 28.

Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.

The most challenging complication associated with Factor VIII (FVIII) replacement therapy is the development of neutralizing anti-drug antibodies, or inhibitors, which occur in 23-35% of severe (FVIII level <1%) hemophilia A (HA) patients and are a serious hindrance to effective management of HA. Consequently, strategies that can either prevent anti-FVIII inhibitors from developing or "tolerize" individuals who develop such antibodies represent a clinically important unmet need. One intervention for patients with high-titer inhibitors is immune tolerance induction (ITI) therapy. Read More

View Article and Full-Text PDF

The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy.

Biologics 2021 7;15:265-277. Epub 2021 Jul 7.

Department of Vascular Surgery, Medical University of Vienna, Vienna, Austria.

Lung cancer has a dismal prognosis and novel targeted therapies leave still room for major improvements and better outcomes. Immunotherapy targeting immune checkpoint (IC) proteins, either as single agents or in combination with chemotherapy, is active but responders constitute only approximately 10-15% of non-small cell lung cancer (NSCLC) patients. Other effector immune cells such as CAR-T cells or NK cells may help to overcome the limitations of the IC inhibitor therapies for lung cancer. Read More

View Article and Full-Text PDF

Combining CD47 blockade with trastuzumab eliminates HER2-positive breast cancer cells and overcomes trastuzumab tolerance.

Proc Natl Acad Sci U S A 2021 Jul;118(29)

Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Cell Research, Stanford University, Stanford, CA 94305;

Trastuzumab, a targeted anti-human epidermal-growth-factor receptor-2 (HER2) monoclonal antibody, represents a mainstay in the treatment of HER2-positive (HER2) breast cancer. Although trastuzumab treatment is highly efficacious for early-stage HER2 breast cancer, the majority of advanced-stage HER2 breast cancer patients who initially respond to trastuzumab acquire resistance to treatment and relapse, despite persistence of HER2 gene amplification/overexpression. Here, we sought to leverage HER2 overexpression to engage antibody-dependent cellular phagocytosis (ADCP) through a combination of trastuzumab and anti-CD47 macrophage checkpoint immunotherapy. Read More

View Article and Full-Text PDF

Dinitrophenol-mediated modulation of an anti-PD-L1 VHH for Fc-dependent effector functions and prolonged serum half-life.

Eur J Pharm Sci 2021 Jul 10;165:105941. Epub 2021 Jul 10.

Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address:

Single-domain antibodies, VHHs or nanobodies, represent a promising set of alternatives to conventional therapeutic antibodies, gaining substantial attention in the field of cancer immunotherapy. However, inherent drawbacks of nanobodies such as fast clearance from blood circulation and lack of immune effector functions often led to unsatisfactory therapeutic efficacy. We previously reported that dinitrophenyl modification of an anti-EGFR VHH conferred Fc-dependent immune effector functions and elongated serum half-life on it through recruiting of hapten antibodies, resulting in improved immunotherapy efficacy in vivo. Read More

View Article and Full-Text PDF

Targeted Mass Spectrometry-Based Approach for the Determination of Intrinsic Internalization Kinetics of Cell-Surface Membrane Protein Targets.

Anal Chem 2021 Jul 13. Epub 2021 Jul 13.

Preclinical and Translational Sciences/Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals Inc., Cambridge, Massachusetts 02139, United States.

Successful development of targeted therapeutics aimed at the elimination of diseased cells relies on the target properties and the therapeutics that target them. Currently, target properties have been evaluated through antibody-dependent semiquantitative approaches such as flow cytometry, Western blotting, or microscopy. Since antibodies can alter target properties following binding, antibody-dependent approaches provide at best skewed measurements for target intrinsic properties. Read More

View Article and Full-Text PDF

Combinatorial immunotherapy of N-803 (IL-15 superagonist) and dinutuximab with ex vivo expanded natural killer cells significantly enhances in vitro cytotoxicity against GD2 pediatric solid tumors and in vivo survival of xenografted immunodeficient NSG mice.

J Immunother Cancer 2021 Jul;9(7)

Department of Pediatrics, New York Medical College, Valhalla, New York, USA

Background: Children with recurrent and/or metastatic osteosarcoma (OS), neuroblastoma (NB) and glioblastoma multiforme (GBM) have a dismal event-free survival (<25%). The majority of these solid tumors highly express GD2. Dinutuximab, an anti-GD2 monoclonal antibody, significantly improved event-free survival in children with GD2 NB post autologous stem cell transplantation and enhanced natural killer (NK) cell-mediated antibody-dependent cell cytotoxicity. Read More

View Article and Full-Text PDF

TIGIT-Fc Promotes Antitumor Immunity.

Cancer Immunol Res 2021 Jul 8. Epub 2021 Jul 8.

Department of Biophysics, Second Military Medical University

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is a checkpoint receptor that mediates both T cell and natural killer (NK) cell exhaustion in tumors. An Fc-TIGIT fusion protein was shown to induce an immune-tolerance effect in a previous report, but the relevance of the TIGIT-Fc protein to tumor immunity is unknown. Here, we found that TIGIT-Fc promotes, rather than suppresses, tumor immunity. Read More

View Article and Full-Text PDF

Dinitrophenol-Hyaluronan Conjugates as Multivalent Antibody-Recruiting Glycopolymers for Targeted Cancer Immunotherapy.

ChemMedChem 2021 Jul 8. Epub 2021 Jul 8.

Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.

Multivalent antibody-recruiting glycopolymers (MARGs) composed of hyaluronic acid (HA) grafted with multiple copies of dinitrophenol (DNP) were developed for targeted cancer immunotherapy. Structure-activity studies demonstrated that the MARGs were able to specifically recognize CD44-positive cancer cells and displayed remarkable antibody-recruiting capacities and tumor cell killing activities dependent on the introduced multivalent effect and the length of PEG linker. One of the MARGs, HA-[PEG -DNP] , showed the best capacity for clustering anti-DNP antibodies onto CD44-positive cancer cells and displayed potent in vitro anti-cancer activity by triggering complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Read More

View Article and Full-Text PDF

The signal pathways and treatment of cytokine storm in COVID-19.

Signal Transduct Target Ther 2021 07 7;6(1):255. Epub 2021 Jul 7.

Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, and the Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

The Coronavirus Disease 2019 (COVID-19) pandemic has become a global crisis and is more devastating than any other previous infectious disease. It has affected a significant proportion of the global population both physically and mentally, and destroyed businesses and societies. Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation of monocytes and macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, and especially, cytokine storm (CS). Read More

View Article and Full-Text PDF

Enhanced ability of plant-derived PGT121 glycovariants to eliminate HIV-1-infected cells.

J Virol 2021 Jul 7:JVI0079621. Epub 2021 Jul 7.

Centre de Recherche du CHUM, Montreal, QC, Canada.

The activity of broadly neutralizing antibodies (bNAbs) targeting HIV-1 depends on pleiotropic functions including viral neutralization and the elimination of HIV-1-infected cells. Several studies have suggested that passive administration of bNAbs represents a valuable strategy for the prevention or treatment of HIV-1. Additionally, different strategies are currently being tested to scale-up the production of bNAbs to obtain the large quantities of antibodies required for clinical trials. Read More

View Article and Full-Text PDF

Determinants of response to daratumumab in Epstein-Barr virus-positive natural killer and T-cell lymphoma.

J Immunother Cancer 2021 Jul;9(7)

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Background: The potential therapeutic efficacy of daratumumab in natural killer T-cell lymphoma (NKTL) was highlighted when its off-label usage produced sustained remission in a patient with highly refractory disease. This is corroborated recently by a phase II clinical trial which established that daratumumab monotherapy is well tolerated and displayed encouraging response in relapsed/refractory NKTL patients. However, little is known regarding the molecular factors central to the induction and regulation of the daratumumab-mediated antitumor response in NKTL. Read More

View Article and Full-Text PDF

High-Density of FcγRIIIA (CD16) Tumor-Associated Neutrophils in Metastases Improves the Therapeutic Response of Cetuximab in Metastatic Colorectal Cancer Patients, Independently of the HLA-E/CD94-NKG2A Axis.

Front Oncol 2021 15;11:684478. Epub 2021 Jun 15.

Department of Pathology, University Hospital of Nantes, Nantes, France.

Antibody-dependent cellular cytotoxicity (ADCC) in the anti-tumor effect of cetuximab in metastatic colorectal cancer (mCRC) is only based on the impact of FcγRIIIA (CD16) polymorphisms as predictive of therapeutic response. However, nature, density and therapeutic impact of FcγRIIIA (CD16) effector cells in tumor remain poorly documented. Moreover, the inhibition of cetuximab-mediated ADCC induced by NK cells by the engagement of the new inhibitory CD94-NKG2A immune checkpoint has only been demonstrated . Read More

View Article and Full-Text PDF

Prospective Artificial Intelligence to Dissect the Dengue Immune Response and Discover Therapeutics.

Front Immunol 2021 15;12:574411. Epub 2021 Jun 15.

Institute of Medical Engineering and Medical Informatics, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland FHNW, Muttenz, Switzerland.

Dengue virus (DENV) poses a serious threat to global health as the causative agent of dengue fever. The virus is endemic in more than 128 countries resulting in approximately 390 million infection cases each year. Currently, there is no approved therapeutic for treatment nor a fully efficacious vaccine. Read More

View Article and Full-Text PDF

Immunological mechanisms of vaccine-induced protection against COVID-19 in humans.

Nat Rev Immunol 2021 Jul 1. Epub 2021 Jul 1.

Telethon Kids Institute, Perth Children's Hospital, University of Western Australia, Nedlands, Western Australia, Australia.

Most COVID-19 vaccines are designed to elicit immune responses, ideally neutralizing antibodies (NAbs), against the SARS-CoV-2 spike protein. Several vaccines, including mRNA, adenoviral-vectored, protein subunit and whole-cell inactivated virus vaccines, have now reported efficacy in phase III trials and have received emergency approval in many countries. The two mRNA vaccines approved to date show efficacy even after only one dose, when non-NAbs and moderate T helper 1 cell responses are detectable, but almost no NAbs. Read More

View Article and Full-Text PDF

Antibodies Elicited in Response to a Single Cycle Glycoprotein D Deletion Viral Vaccine Candidate Bind C1q and Activate Complement Mediated Neutralization and Cytolysis.

Viruses 2021 Jun 30;13(7). Epub 2021 Jun 30.

Departments of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Herpes simplex virus (HSV) prevention is a global health priority but, despite decades of research, there is no effective vaccine. Prior efforts focused on generating glycoprotein D (gD) neutralizing antibodies, but clinical trial outcomes were disappointing. The deletion of gD yields a single-cycle candidate vaccine (∆gD-2) that elicits high titer polyantigenic non-gD antibodies that exhibit little complement-independent neutralization but mediate antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Read More

View Article and Full-Text PDF

NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications.

Int J Mol Sci 2021 Jun 22;22(13). Epub 2021 Jun 22.

Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy.

Key features of chronic lymphocytic leukemia (CLL) are defects in the immune system and the ability of leukemic cells to evade immune defenses and induce immunosuppression, resulting in increased susceptibility to infections and disease progression. Several immune effectors are impaired in CLL, including T and natural killer (NK) cells. The role of T cells in defense against CLL and in CLL progression and immunotherapy has been extensively studied. Read More

View Article and Full-Text PDF

Development of a Macrophage-Based ADCC Assay.

Vaccines (Basel) 2021 Jun 17;9(6). Epub 2021 Jun 17.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Fc-dependent effector functions are an important determinant of the in vivo potency of therapeutic antibodies. Effector function is determined by the combination of FcRs bound by the antibody and the cell expressing the relevant FcRs, leading to antibody-dependent cellular cytotoxicity (ADCC). A number of ADCC assays have been developed; however, they suffer from limitations in terms of throughput, reproducibility, and in vivo relevance. Read More

View Article and Full-Text PDF

Natural Killer Cell Responses during Human γ-Herpesvirus Infections.

Christian Münz

Vaccines (Basel) 2021 Jun 15;9(6). Epub 2021 Jun 15.

Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.

Herpesviruses are main sculptors of natural killer (NK) cell repertoires. While the β-herpesvirus human cytomegalovirus (CMV) drives the accumulation of adaptive NKG2C-positive NK cells, the human γ-herpesvirus Epstein-Barr virus (EBV) expands early differentiated NKG2A-positive NK cells. While adaptive NK cells support adaptive immunity by antibody-dependent cellular cytotoxicity, NKG2A-positive NK cells seem to preferentially target lytic EBV replicating B cells. Read More

View Article and Full-Text PDF

ADCC-Inducing Antibody Trastuzumab and Selection of KIR-HLA Ligand Mismatched Donors Enhance the NK Cell Anti-Breast Cancer Response.

Cancers (Basel) 2021 Jun 28;13(13). Epub 2021 Jun 28.

Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands.

Natural killer (NK)-cell-based immunotherapies are an attractive treatment option for cancer. We previously showed that alloreactive mouse NK cells cured mice of 4T1 breast cancer. However, the tumor microenvironment can inhibit immune responses, and these suppressive factors must be overcome to unfold the NK cells' full anti-tumor potential. Read More

View Article and Full-Text PDF

Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma.

Cancers (Basel) 2021 Jun 20;13(12). Epub 2021 Jun 20.

Laboratory of Hematology, GIGA I3, Department of Hematology, University of Liège, 4000 Liège, Belgium.

Multiple myeloma (MM) is an incurable cancer characterized by the proliferation and accumulation of monoclonal plasma cells in the bone marrow. The monoclonal anti-CD38 daratumumab has taken a central place in the different treatment regimens for newly diagnosed and relapsed, refractory myeloma. In this study, we correlated the NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and potential fratricide induced by daratumumab with CD38-expression levels on both effector and target cells. Read More

View Article and Full-Text PDF

A diverse collection of B cells responded to HIV infection in infant BG505.

Cell Rep Med 2021 Jun 15;2(6):100314. Epub 2021 Jun 15.

Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Increasing evidence suggests infants develop unique neutralizing antibody (nAb) responses to HIV compared to adults. Here, we dissected the nAb response of an infant whose virus is in clinical trials as a vaccine immunogen, with a goal of characterizing the broad responses in the infant to this antigen. We isolated 73 nAbs from infant BG505 and identified a large number of clonal families. Read More

View Article and Full-Text PDF