A5103277533- CAR-T cell therapy research
- Inflammatory Bowel Disease
- Immunotherapy and Immune Responses
- Photoacoustic and Ultrasonic Imaging
- Immune Cell Function and Interaction
- Microscopic Colitis
- Melanoma and MAPK Pathways
- Ultrasound Imaging and Elastography
- Cancer Immunotherapy and Biomarkers
- Ultrasound and Hyperthermia Applications
- Virus-based gene therapy research
- Cancer Genomics and Diagnostics
- Cutaneous Melanoma Detection and Management
- Cytomegalovirus and herpesvirus research
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Nanowire Synthesis and Applications
- Viral gastroenteritis research and epidemiology
- Prostate Cancer Treatment and Research
- Protein Degradation and Inhibitors
- Clostridium difficile and Clostridium perfringens research
- Phagocytosis and Immune Regulation
- Autoimmune and Inflammatory Disorders
- Eosinophilic Esophagitis
Harvard University
2008-2025
Massachusetts Institute of Technology
2010-2025
Broad Institute
2008-2025
Dana-Farber Cancer Institute
2008-2025
Tufts University
2012-2025
University of Michigan
2015-2024
Emory University
2024
Grady Memorial Hospital
2024
Carisma Therapeutics (United States)
2024
CSL (Australia)
2023
Somatic alterations in cellular DNA underlie almost all human cancers. The prospect of targeted therapies and the development high-resolution, genome-wide approaches are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project copy-number primary lung adenocarcinomas. By analysis large collection tumours (n = 371) using dense single nucleotide polymorphism arrays, identify total 57 significantly recurrent events. We find that 26 39 autosomal...
The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T may offer several advantages. We developed a retroviral construct specific for mouse fibroblast activation protein (FAP), comprising single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with CD8α hinge and transmembrane regions, human CD3ζ 4-1BB domains. transduced muFAP-CAR secreted IFN-γ killed...
A chimeric antigen receptor redirects T cells to treat glioblastoma.
NUT midline carcinoma (NMC) is a uniformly lethal malignancy that defined by rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14. NMCs are morphologically indistinguishable from other poorly differentiated carcinomas, and diagnosis usually made currently fluorescence situ hybridization (FISH). As normal expression confined to ovary, we reasoned an immunohistochemical (IHC) stain for would be useful diagnosing NMC. To this end, raised highly specific rabbit...
Abstract Single and dual amino acid substitution variants were generated in the TCR CDRs of three TCRs that recognize tumor-associated Ags. Substitutions enhance reactivity gene-modified T cells to cognate Ag complex identified using a rapid RNA-based transfection system. The screening panel 1G4 TCR, recognizes peptide corresponding residues 157–165 human cancer testis NY-ESO-1 (SLLMWITQC) context HLA-A*02 class I allele, resulted identification single CDR3α CDR2β substitutions dramatically...
BackgroundThe majority of prostate cancers harbor gene fusions the 5′-untranslated region androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation–specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated a more aggressive clinical phenotype, implying existence distinct subclass cancer defined by this fusion.
Abstract Cell-based antitumor immunity is driven by CD8+ cytotoxic T cells bearing TCR that recognize specific tumor-associated peptides bound to class I MHC molecules. Of several cellular proteins involved in cell:target-cell interaction, the determines specificity of binding; however, relative amount its contribution avidity remains unknown. To study relationship between affinity and avidity, with intent identifying optimal for gene therapy, we derived 24 MART-1:27-35 (MART-1) melanoma...
No curative treatment exists for glioblastoma, with median survival times of less than 2 years from diagnosis. As an approach to develop immune-based therapies we sought target antigens expressed in glioma stem cells (GSCs). GSCs have multiple properties that make them significantly more representative tumors established cell lines. Epidermal growth factor receptor variant III (EGFRvIII) is the result a novel tumor-specific gene rearrangement produces unique protein approximately 30%...
Global studies of transcript structure and abundance in cancer cells enable the systematic discovery aberrations that contribute to carcinogenesis, including gene fusions, alternative splice isoforms, somatic mutations. We developed a approach characterize spectrum cancer-associated mRNA alterations through integration transcriptomic structural genomic data, we applied this generate new insights into melanoma biology. Using paired-end massively parallel sequencing cDNA (RNA-seq) together...
Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed both tumors normal tissues have led significant toxicity. Preclinical studies limited by the use of xenograft models do not adequately recapitulate system clinically relevant host. A constitutively activated mutant naturally occurring epidermal growth factor (EGFRvIII) is antigenically...
T cells expressing antigen-specific T-cell receptors (TCRs) can mediate effective tumor regression, but they often also are accompanied by autoimmune responses. To determine the TCR affinity threshold defining optimal balance between antitumor activity and autoimmunity in vivo , we used a unique self-antigen system comprising seven human melanoma gp100(209–217)-specific TCRs spanning physiological affinities (1–100 μM). We found that vitro responses determined affinity, except one case was...
Abstract Purpose: Fusion of the TMPRSS2 prostate-specific gene with ERG transcription factor is a putatively oncogenic rearrangement that commonly found in prostate cancer tissue from men undergoing prostatectomy. However, prevalence fusion was less common samples transurethral resection Swedish cohort patients incidental followed by watchful waiting, raising question as to whether high prostatectomy specimens reflects selection bias. We sought determine TMPRSS2-ERG among antigen–screened...
Ras homolog gene family, member A (RhoA)/Rho-associated coiled-coil forming protein kinase signaling is a key pathway in multiple types of solid organ fibrosis, including intestinal fibrosis. However, the pleiotropic effects RhoA/Rho-associated have frustrated targeted drug discovery efforts. Recent recognition role Rho-regulated transcription by serum response factor (SRF) and its transcriptional cofactor myocardin-related (MRTF-A) suggest novel locus for pharmacological...