Abstract:
:Disialoganglioside GD2 is an important target on several pediatric and adult cancer types including neuroblastoma, retinoblastoma, melanoma, small-cell lung cancer, brain tumors, sarcomas, and cancer stem cells. We have utilized structural and computational methods to refine the framework of humanized monoclonal antibody 3F8, the highest affinity anti-GD2 antibody in clinical development. Two constructs (V3 and V5) were designed to enhance stability and minimize potential immunogenicity. Construct V3 contained 12 point mutations and had higher thermal stability and comparable affinity and in vitro tumor cells killing as the parental hu3F8. Construct V5 had nine point mutations to minimize potential immunogenicity, but resulted in weaker thermal stability, weaker antigen binding, and reduced tumor killing potency. When construct V3 was combined with the single point mutation HC:G54I, the resulting V3-Ile construct had enhanced stability, antigen binding, and a nearly sixfold increase in tumor cell killing. The resulting product is a lead candidate for clinical development for the treatment of GD2-positive tumors.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Ahmed M,Hu J,Cheung NKdoi
10.3389/fimmu.2014.00372subject
Has Abstractpub_date
2014-08-14 00:00:00pages
372issn
1664-3224journal_volume
5pub_type
杂志文章abstract::Human noroviruses (HuNoVs) are the cause of more than 95% of epidemic non-bacterial gastroenteritis worldwide, with some lethal cases. These viral agents affect people of all ages. However, young children and older adults are the highest-risk groups, being affected with the greatest rate of hospitalizations and morbid...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00961
更新日期:2020-06-16 00:00:00
abstract::Considerable evidence has been gathered over the last 10 years showing that the tumor microenvironment (TME) is not simply a passive recipient of immune cells, but an active participant in the establishment of immunosuppressive conditions. It is now well documented that hypoxia, within the TME, affects the functions o...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2013.00490
更新日期:2013-12-25 00:00:00
abstract::Breast cancer is characterized by cellular and molecular heterogeneity. Several molecular events are involved in controlling malignant cell process. In this sense, the importance of studying multiple cell alterations in this pathology is overriding. A well-identified fact on immune response is that it can vary depend ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00348
更新日期:2019-03-01 00:00:00
abstract::Ectoenzyme and receptor BST-1/CD157 has been considered as a key molecule involved in the regulation of functional activity of cells in various tissues and organs. It is commonly accepted that CD157 catalyzes NAD+ hydrolysis and acts as a component of integrin adhesion receptor complex. Such properties are important f...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.585294
更新日期:2020-11-10 00:00:00
abstract::Human cytomegalovirus (HCMV) is under constant selective pressure from the immune system in vivo. Study of HCMV genes that have been lost in the absence of, or genetically altered by, such selection can focus research toward findings of in vivo significance. We have been particularly interested in the most pronounced ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02214
更新日期:2018-10-01 00:00:00
abstract::Dyslipidemia is a central component of atherosclerosis and metabolic syndrome linked to chronic inflammation and immune dysfunction. Previously, we showed that hypercholesterolemic apolipoprotein E knock out (apoE-/-) mice exhibit systemic effects including skin inflammation and hypertrophic lymph nodes (LNs). However...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00575
更新日期:2019-03-27 00:00:00
abstract::Cytotoxic T lymphocytes and NK cells play an important role in eliminating malignant tumor cells and the number and activity of tumor-infiltrating T cells represent a good marker for tumor prognosis. Based on these findings, immunotherapy, e.g., checkpoint blockade, has received considerable attention during the last ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00248
更新日期:2017-03-08 00:00:00
abstract:Background:The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary approach to affect gut microbiota composition and improv...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01443
更新日期:2017-12-12 00:00:00
abstract::There is accumulating evidence to indicate that long non-coding RNAs (lncRNAs) are important regulators of the inflammatory response. In this report, we have employed next generation sequencing to identify 14 lncRNAs that are differentially expressed in human lung fibroblasts following the induction of inflammation us...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02906
更新日期:2018-12-11 00:00:00
abstract::Acute pancreatitis (AP) is a common and devastating inflammatory disorder of the pancreas. However, there are still no effective treatments available for the disease. Therefore, it is important to discover new therapeutic targets and strategies for better treatment and prognosis of AP patients. Toll-like receptor 3 (T...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00980
更新日期:2019-05-03 00:00:00
abstract::Cancer immunotherapy (CIT) with antibodies targeting the programmed cell death 1 protein (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis have changed the standard of care in multiple cancers. However, durable antitumor responses have been observed in only a minority of patients, indicating the presence of other i...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.598877
更新日期:2020-11-05 00:00:00
abstract:OBJECTIVE:Roseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. h...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01166
更新日期:2017-09-26 00:00:00
abstract::Immune activation is the driving force behind the occurrence of AIDS and non-AIDS events, and is only partially reduced by antiretroviral therapy (ART). Soon after HIV infection, intestinal CD4+ T cells are depleted leading to epithelial gut damage and subsequent translocation of microbes and/or their products into sy...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00465
更新日期:2019-03-18 00:00:00
abstract::Intercellular communication is crucial to the immune system response. In the recent years, the discovery of exosomes has changed the way immune response orchestration was understood. Exosomes are able to operate as independent units that act as mediators in both physiological and pathological conditions. These structu...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00826
更新日期:2017-07-21 00:00:00
abstract::Transcriptional activation and repression of genes that are developmentally regulated or exhibit cell-type specific expression patterns is largely achieved by modifying the chromatin template at a gene locus. Complex formation of stable epigenetic histone marks, loss or gain of DNA methylation, alterations in chromoso...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00112
更新日期:2013-05-16 00:00:00
abstract::Studies to develop cell-based therapies for cancer and other diseases have consistently shown that purified human natural killer (NK) cells secrete cytokines and kill target cells after in vitro culture with high concentrations of cytokines. However, these assays poorly reflect the conditions that are likely to prevai...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00101
更新日期:2016-03-22 00:00:00
abstract::Outcomes in stem cell transplantation (SCT) are modeled using probability theory. However, the clinical course following SCT appears to demonstrate many characteristics of dynamical systems, especially when outcomes are considered in the context of immune reconstitution. Dynamical systems tend to evolve over time acco...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00613
更新日期:2014-12-03 00:00:00
abstract::Formation of pathological anti-FVIII antibodies, or "inhibitors," is the most serious complication of therapeutic FVIII infusions, affecting up to 1/3 of severe Hemophilia A (HA) patients. Inhibitor formation is a classical T-cell dependent adaptive immune response. As such, it requires help from the innate immune sys...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01219
更新日期:2020-06-12 00:00:00
abstract::Immunoglobulin (Ig) replacement therapy dramatically changed the clinical course of primary hypogammaglobulinemias, significantly reducing the incidence of infectious events. Over the last two decades its use has been extended to secondary antibody deficiencies, particularly those related to hematological disorders as...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00626
更新日期:2014-12-08 00:00:00
abstract::We recently reported that the treatment with nanoparticles (NPs) loaded with tolerogenic cytokines suppressed the manifestations of lupus-like disease induced by the transfer of donor CD4+ T cells from DBA/2 mice into (C57BL/6 × DBA/2)F1 (BDF1) mice. Although the protective effects were ascribed to the induction of ad...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.583338
更新日期:2020-12-16 00:00:00
abstract::Soluble factors are an essential means of communication between cells and their environment. However, many molecules readily interact with extracellular matrix components, giving rise to multiple modes of diffusion. The molecular quantification of diffusion in situ is thus a challenging imaging frontier, requiring ver...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01073
更新日期:2018-05-22 00:00:00
abstract::New vaccine design approaches would be greatly facilitated by a better understanding of the early systemic changes, and those that occur at the site of injection, responsible for the installation of a durable and oriented protective response. We performed a detailed characterization of very early infection and host re...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00870
更新日期:2018-04-25 00:00:00
abstract::There is far less information available about the tumor infiltrating B (TIL-B) cells, than about the tumor infiltrating T cells. We focused on discovering the features and potential role of B lymphocytes in solid tumors. Our project aimed to develop innovative strategies to define cancer membrane structures. We chose ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00650
更新日期:2019-04-05 00:00:00
abstract::Stromal cells are a subject of rapidly growing immunological interest based on their ability to influence virtually all aspects of innate and adaptive immunity. Present in every bodily tissue, stromal cells complement the functions of classical immune cells by sensing pathogens and tissue damage, coordinating leukocyt...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01093
更新日期:2019-05-15 00:00:00
abstract::The intestinal microbiota, composed of a large population of microorganisms, is often considered a "forgotten organ" in human health and diseases. Increasing evidence indicates that dysbiosis of the intestinal microbiota is closely related to colorectal cancer (CRC). The roles for intestinal microorganisms that initia...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.615056
更新日期:2020-11-30 00:00:00
abstract::Antigen capturing at the periphery is one of the earliest, crucial functions of antigen-presenting cells (APCs) to initiate immune responses. Langerhans cells (LCs), the epidermal APCs migrate to draining lymph nodes (DLNs) upon acquiring antigens. An arsenal of endocytic molecules is available to this end, including ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00744
更新日期:2020-04-27 00:00:00
abstract::Donor-specific anti-HLA antibodies (DSAs) are a major risk factor associated with renal allograft outcomes. As a trigger of B cell antibody production, T follicular helper cells (Tfhs) promote DSA appearance. Herein, we evaluated whether circulating Tfhs (cTfhs) are associated with the genesis of antibody-mediated rej...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02071
更新日期:2019-09-10 00:00:00
abstract::Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 checkpoint interventi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01769
更新日期:2018-07-30 00:00:00
abstract:Background:Endoplasmic reticulum lipid raft-associated protein 2 (ERLIN2) is protein contained in the membrane of the endoplasmic reticulum. In lung adenocarcinoma (LUAD), the molecular function of ERLIN2 and the correlation between ERLIN2 and tumor-infiltrating immune cells have been unclear. The aim of our study was ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.568440
更新日期:2020-12-07 00:00:00
abstract::The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The closing of borders, the reduction of people transit and the confinement of the...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.573179
更新日期:2020-10-15 00:00:00