A5064129992- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Bacterial Genetics and Biotechnology
- Genomics and Phylogenetic Studies
- Plant tissue culture and regeneration
- Microbial Natural Products and Biosynthesis
- Monoclonal and Polyclonal Antibodies Research
- Neurogenesis and neuroplasticity mechanisms
- COVID-19 Clinical Research Studies
- Cyclization and Aryne Chemistry
- Protein Degradation and Inhibitors
- Gene Regulatory Network Analysis
- Viral Infectious Diseases and Gene Expression in Insects
- Immune responses and vaccinations
- Genetics and Neurodevelopmental Disorders
- Virus-based gene therapy research
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
TScan Therapeutics (United States)
2020-2024
Massachusetts Institute of Technology
2018-2022
Broad Institute
2021
Centralized facilities for genetic engineering, or "biofoundries", offer the potential to design organisms address emerging needs in medicine, agriculture, industry, and defense. The field has seen rapid advances technology, but it is difficult gauge current capabilities identify gaps across projects. To this end, our foundry was assessed via a timed "pressure test", which 3 months were given build produce 10 molecules unknown us advance. By applying diversity of new approaches, we produced...
Abstract Development of effective strategies to detect, treat, or prevent COVID-19 requires a robust understanding the natural immune response SARS-CoV-2, including cellular mediated by T cells. We used an unbiased, genome-wide screening technology, termed T-Scan, identify specific epitopes in SARS-CoV-2 that are recognized memory CD8+ cells 25 convalescent patients, focusing on presented six most prevalent HLA types: A*02:01, A*01:01, A*03:01, A*11:01, A*24:02, and B*07:02. For each type,...
Abstract Motivation Applications in synthetic and systems biology can benefit from measuring whole-cell response to biochemical perturbations. Execution of experiments cover all possible combinations perturbations is infeasible. In this paper, we present the host model (HRM), a machine learning approach that maps single transcriptional combination Results The HRM combines high-throughput sequencing with infer links between experimental context, prior knowledge cell regulatory networks,...
Development of effective strategies to detect, treat, or prevent COVID-19 requires a robust understanding natural immunity SARS-CoV-2, including the cellular response mediated by T cells. We used an unbiased, genome-wide screening technology comprehensively identify specific epitopes in SARS-CoV-2 that are recognized memory CD8+ cells 25 convalescent patients. For each six HLA types examined, patient 3–8 immunodominant broadly shared among patients, and single-cell sequencing revealed common...
Sequencing technologies, in particular RNASeq, have become critical tools the design, build, test and learn cycle of synthetic biology. They provide a better understanding designs, they help identify ways to improve select designs. While these data are beneficial their collection analysis is complex, multistep process that has implications on both discovery reproducibility experiments. Additionally, tool parameters, experimental metadata, normalization standardization file formats present...
Abstract Applications in synthetic and systems biology can benefit from measuring whole-cell response to biochemical perturbations. Execution of experiments cover all possible combinations perturbations is infeasible. In this paper, we present the host model (HRM), a machine learning approach that takes cell single as input predicts whole transcriptional combination inducers. We find HRM able qualitatively predict directionality dysregulation inducers with an accuracy >90% using data...
<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> 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> 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....
<h3>Background</h3> Approximately 30–40% of AML patients relapse following allogeneic hematopoietic stem cell transplant therapy, leaving them with very few treatment options.<sup>1 2</sup> Rare that naturally develop an HA-1-specific graft-versus-leukemia T response, however, show substantially lower rates.<sup>3 4</sup> HA-1 (VLHDDLLEA, genotype RS_1801284 A/G or A/A) is HLA-A*02:01-and hematopoietically restricted minor histocompatibility antigen, making it ideal candidate for TCR...