A5056008039- Multiple Myeloma Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- Fibroblast Growth Factor Research
- Genetic Syndromes and Imprinting
- Synthesis and Biological Evaluation
- Protein Tyrosine Phosphatases
- Prenatal Screening and Diagnostics
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Tryptophan and brain disorders
- Lymphoma Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
- Advanced Biosensing Techniques and Applications
- Neutropenia and Cancer Infections
- Cancer Mechanisms and Therapy
- Nicotinic Acetylcholine Receptors Study
Janssen (United States)
2015-2025
AbbVie (United States)
2024
Vrije Universiteit Amsterdam
2022-2023
Johnson & Johnson (Sweden)
2023
Janssen (Belgium)
2021-2023
Amsterdam University Medical Centers
2023
Janssen (Ireland)
2023
Utrecht University
2022
Tennessee Oncology
2022
Sarah Cannon
2022
Teclistamab is a T-cell–redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen myeloma cells. In phase 1 dose-defining portion study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma.
Preimplantation development is a period of dynamic epigenetic change that begins with remodeling egg and sperm genomes, ends implantation. During this time, parental-specific imprinting marks are maintained to direct appropriate imprinted gene expression. We previously demonstrated H19 could be lost during preimplantation under certain culture conditions. To define the lability genomic imprints determine whether loss continues at later stages development, expression methylation were examined...
G protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate killing of GPRC5D-expressing myeloma cells.In phase 1 study, we evaluated talquetamab administered intravenously weekly or every other week (in doses from 0.5 180 μg per kilogram body weight) subcutaneously weekly, week, monthly (5 1600 kilogram) patients who had heavily pretreated...
Abstract Cell surface expression levels of GPRC5D, an orphan G protein–coupled receptor, are significantly higher on multiple myeloma (MM) cells, compared with normal plasma cells or other immune which renders it a promising target for immunotherapeutic strategies. The novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D+ MM cell lines in the presence T from both healthy donors heavily pretreated patients. In addition, talquetamab has potent...
8011 Background: Teclistamab is the first approved off-the-shelf BCMA×CD3 bispecific antibody for treatment of patients (pts) with RRMM based on data from pivotal phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098). Moreau et al ( NEJM 2022) reported rapid, deep, and durable responses: overall response rate (ORR) was 63% (39% ≥complete [CR] rate), a median duration (mDOR) 18.4 mo, progression-free survival (mPFS) 11.3 mo after follow-up (mFU) 14.1 mo. Here, we present updated results...
E2F is a family of transcription factors that regulate both cellular proliferation and differentiation. To establish the role E2F3 in vivo, we generated an E2f3 mutant mouse strain. E2F3-deficient mice arise at one-quarter expected frequency, demonstrating important for normal development. determine molecular consequences deficiency, analyzed properties embryonic fibroblasts derived from mice. Mutation dramatically impairs mitogen-induced, transcriptional activation numerous E2F-responsive...
Cloning by somatic cell nuclear transfer requires that epigenetic information possessed the donor nucleus be reprogrammed to an embryonic state. Little is known, however, about this remodeling process, including when it occurs, its efficiency, and how well markings characteristic of normal development are maintained. Examining fate associated with imprinted genes during clonal offers one means addressing these questions. We examined transcript abundance, allele specificity gene expression,...
E2F directs the cell cycle-dependent expression of genes that induce or regulate division process. In mammalian cells, this transcriptional activity arises from combined properties multiple E2F-DP heterodimers. study, we show potential individual species is dependent upon their nuclear localization. This a constitutive property E2F-1, -2, and -3, whereas localization E2F-4 its association with other factors. We previously showed accounts for majority endogenous species. now subcellular...
The E2F family of proteins is required to establish the correct cell-cycle-dependent transcription genes that direct process cell division. All previously identified can act in a similar manner; depending on whether or not they are associated with cycle inhibitors retinoblastoma protein (pRB), p107, p130, either repress activate E2F-responsive genes. We now report cloning and characterization another member, E2F-6, whose structure reminiscent dominant other factor families. dimerization DNA...
Efficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment to control cancer progression. In this study, we demonstrate that dual targeting of myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation antigen-presenting cells with agonist anti-CD40 treatment confers superior efficacy increased survival compared monotherapy preclinical models. Concurrent CSF-1R blockade CD40 agonism lead profound changes composition...
Abstract The success of targeted or immune therapies is often hampered by the emergence resistance and/or clinical benefit in only a subset patients. We hypothesized that combining therapy with modulation would show enhanced antitumor responses. Here, we explored combination potential erdafitinib, fibroblast growth factor receptor (FGFR) inhibitor under development, PD-1 blockade an autochthonous FGFR2K660N/p53mut lung cancer mouse model. Erdafitinib monotherapy treatment resulted...
Highlights•Evaluation of gene signatures to predict response immunotherapy in NSCLC.•An EMT/Inflammation score was highly predictive and survival ICB.•Identifies potential role EMT primary resistance NSCLC.AbstractObjectivesTreatment non-small cell lung cancer (NSCLC) with immune checkpoint blockade (ICB) has resulted striking clinical responses, but only a subset patients. The goal this study evaluate transcriptional previously reported the literature an independent cohort NSCLC patients...
Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, demonstrated an overall response rate of 63.0% in 165 heavily pretreated patients with relapsed or refractory multiple myeloma the phase 1/2 MajesTEC-1 study. Cytokine release syndrome (CRS), known manifestation T-cell redirection, was observed 119 (72.1%).Patients received once-weekly teclistamab 1.5 mg/kg subcutaneously after two step-up doses (0.06 and 0.3 mg/kg). CRS graded according to American Society for...
Abstract Background Patients with relapsed/refractory multiple myeloma are at increased risk of infection. Infections during treatment teclistamab, the first B‐cell maturation antigen‐directed bispecific antibody approved for triple‐class–exposed myeloma, was examined in phase 1/2 MajesTEC‐1 study. Methods ( N = 165) received subcutaneous teclistamab 1.5 mg/kg weekly after a step‐up dosing schedule (0.06 and 0.3 mg/kg, each separated by 2–4 days). were monitored frequently infections;...
Teclistamab and other B-cell maturation antigen (BCMA)-targeting bispecific antibodies (BsAbs) have substantial activity in patients with heavily pretreated multiple myeloma (MM) but are associated a high rate of infections. BCMA is also expressed on normal plasma cells mature B cells, which essential for the generation humoral immune response. The aim this study was to improve understanding impact BCMA-targeting BsAbs immunity. teclistamab polyclonal immunoglobulins cell counts evaluated MM...
Abstract Purpose: Bispecific antibodies (BsAb) directed against B-cell maturation antigen (teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated patients with multiple myeloma. However, mechanisms underlying primary acquired resistance remain poorly understood. Experimental Design: The anti–multiple myeloma activity of teclistamab talquetamab was evaluated bone marrow (BM) samples from T-cell phenotype function were...
Abstract Teclistamab is a B-cell maturation antigen (BCMA)–directed bispecific antibody approved for the treatment of patients with triple-class exposed relapsed/refractory multiple myeloma (R/RMM). In phase 1/2 MajesTEC-1 study, cohort who had prior BCMA-targeted therapy (antibody-drug conjugate [ADC] or chimeric receptor T-cell [CAR-T] therapy) was enrolled to explore teclistamab in previously anti-BCMA treatment. At median follow-up 28.0 months (range, 0.7-31.1), 40 received subcutaneous...
Abstract Teclistamab, an off-the-shelf B-cell maturation antigen (BCMA) × CD3 bispecific antibody that mediates T-cell activation and subsequent lysis of BCMA-expressing myeloma cells, is approved for the treatment patients with relapsed/refractory multiple (R/RMM). As a redirection therapy, clinical outcomes teclistamab may be influenced by patient immune fitness tumor expression. We correlated characteristics baseline profiles response disease burden in R/RMM from pivotal phase 1/2...
Tumor development is dependent upon the inactivation of two key tumor-suppressor networks, p16 Ink4a –cycD/cdk4–pRB–E2F and p19 Arf –mdm2–p53, that regulate cellular proliferation tumor surveillance response. These networks are known to intersect with one another, but mechanisms poorly understood. Here, we show E2F directly participates in transcriptional control both normal transformed cells. This occurs a manner significantly different from regulation classic E2F-responsive targets. In...
TIM-3 (T cell immunoglobulin and mucin-domain containing protein 3) is a member of the TIM family proteins that preferentially expressed on Th1 polarized CD4+ CD8+ T cells. Recent studies indicate serves as negative regulator function (i.e. dependent immune responses, proliferation, tolerance, exhaustion). Despite having no recognizable inhibitory signaling motifs, intracellular tail apparently indispensable for function. Specifically, conserved residues Y265/Y272 surrounding amino acids...