A5070149195- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Estrogen and related hormone effects
- Chemokine receptors and signaling
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Effects and risks of endocrine disrupting chemicals
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Lanthanide and Transition Metal Complexes
- Statistical and Computational Modeling
- Neuroendocrine Tumor Research Advances
- Genomic variations and chromosomal abnormalities
- Advanced Polymer Synthesis and Characterization
- IgG4-Related and Inflammatory Diseases
- NF-κB Signaling Pathways
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Organometallic Complex Synthesis and Catalysis
- Gastrointestinal disorders and treatments
- Cancer, Stress, Anesthesia, and Immune Response
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
TScan Therapeutics (United States)
2020-2024
BioNTech (United States)
2021
Merrimack Pharmaceuticals (United States)
2019
Institut de Recherche en Santé, Environnement et Travail
2011-2014
Structure Fédérative de Recherche en Biologie et Santé de Rennes
2013-2014
Inserm
2013-2014
Université de Rennes
2010-2014
Tufts Medical Center
2014
Molecular Oncology (United States)
2014
Centre National de la Recherche Scientifique
2010-2011
CXCR4 and CXCR7 are the two receptors for chemokine CXCL12, a key mediator of growth effect estrogens (E2) in estrogen receptor (ER)-positive breast cancers. In this study we examined E2-regulation CXCL12 axis components their involvement cancer cells. were differentially regulated by E2 which enhanced expression both but repressed CXCR7. Formaldehyde-associated isolation regulatory elements (FAIRE) revealed that E2-mediated transcriptional regulation these genes is linked to control...
Oncogenic mutations in KRAS can be recognized by T cells on specific class I human leukocyte antigen (HLA-I) molecules, leading to tumor control. To date, the discovery of cell targets from has relied occasional responses patient samples or use transgenic mice. overcome these limitations, we have developed a systematic target and validation pipeline. We evaluate presentation mutant peptides individual HLA-I molecules using targeted mass spectrometry identify 13 unpublished KRASG12C/D/R/V...
The orphan receptors COUP-TF (chicken ovalbumin upstream promoter transcription factor) I and II are members of the nuclear receptor superfamily that play distinct critical roles in vertebrate organogenesis. involvement COUP-TFs cancer development has recently been suggested by several studies but remains poorly understood. MCF-7 breast cells overexpressing COUP-TFI human tumors were used to investigate role regulation CXCL12/CXCR4 signaling axis relation cell growth migration. We...
Activation of the Met receptor tyrosine kinase, either by its ligand, hepatocyte growth factor (HGF), or via ligand-independent mechanisms, such as MET amplification overexpression, has been implicated in driving tumor proliferation, metastasis, and resistance to therapy. Clinical development Met-targeted antibodies challenging, however, bivalent exhibit agonistic properties, whereas monovalent lack potency capacity down-regulate Met. Through computational modeling, we found that a antibody...
Abstract Several methods have been developed to evaluate and quantify the effects of Endocrine disruptor chemicals (EDC). Nevertheless, most these are time‐consuming or not enough sensitive detect EDC at environmental range. To link biological effect tested natural protein secretion, we a new screening method based on secretion cytokine CXCL12 (or SDF‐1, Stroma‐cell Derived Factor 1), which plays capital role in cell survival migration. We demonstrated that is regulated by estrogenic...
The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily that play distinct critical roles in vertebrate organogenesis, as demonstrated by loss-of-function and/or mutant mice. Although COUP-TFs expressed a wide range tissues adults, little is known about their functions at later stages development or organism homeostasis. cancer cell lines various origins increasing studies suggest they fate determination and, potentially, progression. Nevertheless, exact...
Both cyclin D1 and the transcription factor C/EBPβ are required for mammary epithelial cell differentiation; however, pathway in which they operate is uncertain. Previous analyses of patterns gene expression human tumors suggested a connection between overexpression C/EBPβ, but whether this represents cancer-specific gain function unknown. an intronless encoding three protein isoforms—LAP1, LAP2, LIP. Here, we provide evidence that engages isoform-specific manner. Cyclin binds to LAP1, event...
<h3>Background</h3> TCR-engineered T cell therapy has shown encouraging response rates in solid tumors, but complete responses are rare and partial often short-lived. We submit that the primary reason underlying these results is tumors exhibit heterogeneous target expression HLA loss common. Consequently, tumor cells lack or lose targeted antigen resistant to single-targeted TCR-T therapies drive relapse. To address challenges, TScan developed clinical trial assays assess patient tumors....
<h3>Background</h3> While T cell receptor (TCR)-engineered (TCR-T) therapy has transformed the landscape of cancer immunotherapy, efficacy and durability response are often limited by tumor heterogeneity, antigenic escape, loss heterozygosity. Treatment solid tumors with multiple TCR-Ts specific for different antigens restricted to several human leukocyte (HLAs) is a promising strategy overcome immune evasion, potentially increase TCR-T therapy. MAGE-A4 expressed in malignancies, including...
<h3>Background</h3> Intratumor antigen heterogeneity represents a major challenge to targeted cancer therapies, including T cell receptor (TCR)-engineered (TCR-T) adoptive therapy. Not every in tumor expresses given tumor-associated and cells lacking the protein will inevitably drive relapse. Furthermore, loss of heterozygosity at human leukocyte (HLA) locus can render resistant TCR-T therapy restricted affected HLA. To address these challenges, TScan is building an ImmunoBank therapeutic...
<h3>Background</h3> The ability to identify problematic off-targets is critical for TCR-T therapies as TCRs that recognize expressed at high levels in organs could cause toxicities. require a fully human system appropriately de-risk their use clinical studies. paucity of relevant animal models detect potential off-target activity has led reliance on predictive computational algorithms guided by positional scanning mutagenesis. These methods fail screen against with low sequence homology...
<h3>Background</h3> Adoptive cell transfer with genetically engineered T cells holds great promise for treating solid tumors. To date, clinical investigations of TCR-engineered therapies (TCR-T) have targeted one antigen at a time and produced response rates ranging from 30-50%. Unfortunately, complete responses been rare, are often short-lived. One possible reason why patients rapidly relapse is that their tumors exhibit substantial heterogeneity expression: not every cancer within tumor...
2554 Background: Checkpoint immunotherapies have revolutionized the treatment of solid tumors yet durably benefit a minority patients because they rely on endogenous anti-tumor T cells. In lacking functional cells, solution is engineering their cells with exogenous cell receptors (TCRs) to efficiently target and kill tumor Initial clinical trials TCR engineered therapies (TCR-Ts) only produced partial, short-lasting responses targeted single antigens. Solid are notoriously heterogenous not...
<h3>Background</h3> Engineered T cell therapy holds great promise for treating solid tumors. To date, clinical investigations of TCR-T therapies have targeted one antigen/HLA at a time and produced encouraging but partial response rates with limited durations. While heterogeneity antigen expression is appreciated as likely driver patient relapse, the contribution HLA loss heterozygosity (LOH), occurring in up to 40% tumors, only now gaining attention. address both LOH requires collection...
<h3>Background</h3> Checkpoint immunotherapies have revolutionized solid tumor treatment yet durably benefit a minority of patients, as they rely on endogenous anti-tumor T cells. A potential solution for patients lacking functional cells is engineering their with exogenous cell receptors (TCRs) to target and kill Initial clinical trials TCR engineered therapies (TCR-Ts) produced partial, short-lasting responses because targeted single antigens. Solid tumors are notoriously heterogenous...
<h3>Background</h3> T-Plex is an autologous TCR-T cell therapy product comprising customized combinations of 2–3 components that recognize different tumor antigens presented on specific HLA class I molecules. Each component engineered using a transposon-based vector encoding the therapeutic TCR, CD8α and CD8β co-receptors, CD34 epitope tag, dominant-negative TGFβRII (DN-TGFβRII), mutated form dihydrofolate reductase (DHFRdm). TSC-200-A0201 intended for treatment HPV16+ HLA-A*02:01+ cancers....