- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Diversity and Career in Medicine
- Monoclonal and Polyclonal Antibodies Research
- Jewish and Middle Eastern Studies
- Immune Cell Function and Interaction
- Multiple Myeloma Research and Treatments
- Jewish Identity and Society
- Prion Diseases and Protein Misfolding
- Dental Education, Practice, Research
- Historical Economic and Social Studies
- European and International Law Studies
- Advances in Oncology and Radiotherapy
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Shakespeare, Adaptation, and Literary Criticism
- Theatre and Performance Studies
- Poetry Analysis and Criticism
- CRISPR and Genetic Engineering
- Health and Medical Research Impacts
- Contemporary Literature and Criticism
- Antibiotic Resistance in Bacteria
- Diverse Musicological Studies
- Literature: history, themes, analysis
- Surgical Simulation and Training
Adaptimmune (United Kingdom)
2010-2023
Celldex Therapeutics (United States)
2016
RCVS Knowledge
2013
Immunocore (United Kingdom)
2012
National Institute for Medical Research
2001
The Pirbright Institute
1999
Northwest Missouri State University
1996
King's College School
1991
Cell Technology (China)
1983
University of Leicester
1983
T cells engineered to express affinity-enhanced TCRs directed a MAGE A3 peptide cross-react with similar, but unrelated, self-peptide.
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...
Abstract We examined the activity of human T cells engineered to express variants a single TCR (1G4) specific for cancer/testis Ag NY-ESO-1, generated by bacteriophage display with wide range affinities (from 4 μM 26 pM). CD8+ expressing intermediate- and high-affinity 1G4 bound NY-ESO-1/HLA-A2 tetramers high avidity specificity, but increased affinity was associated loss target cell specificity gene-modified cells. highest (KD value pM) completely lost specificity. The TCRs in midrange, KD...
Summary Antigen-specific T cell receptor (TCR) gene transfer via patient-derived cells is an attractive approach to cancer therapy, with the potential circumvent immune regulatory networks. However, high-affinity tumour-specific TCR clonotypes are typically deleted from available repertoire during thymic selection because vast majority of targeted epitopes derived autologous proteins. This process places intrinsic constraints on efficacy cell-based vaccines and therapeutic strategies that...
Patients with hepatocellular carcinoma (HCC) have a poor prognosis and limited therapeutic options. Alpha‐fetoprotein (AFP) is often expressed at high levels in HCC an established clinical biomarker of the disease. Expression AFP nonmalignant liver can occur, particularly subset progenitor cells during chronic inflammation, typically lower than HCC. This cancer‐specific overexpression indicates that may be promising target for immunotherapy. We verified expression normal diseased tissue...
Summary CD4+ T helper cells are a valuable component of the immune response towards cancer. Unfortunately, natural tumour-specific occur in low frequency, express relatively low-affinity cell receptors (TCRs) and show poor reactivity cognate antigen. In addition, lack human leucocyte antigen (HLA) class II expression on most cancers dictates that these often unable to respond tumour directly. These deficiencies can be overcome by transducing primary with HLA I-restricted TCRs prior adoptive...
Certain polysulphated polyanions have been shown to prophylactic effects on the progression of transmissible spongiform encephalopathy disease, presumably because they bind prion protein (PrP). Until now, difficulty obtaining large quantities native PrP has precluded detailed studies these interactions. We over-expressed murine recombinant (recPrP), lacking its glycophosphoinositol membrane anchor, in modified mammalian cells. Milligram secreted, soluble and partially glycosylated were...
Tumor-associated human telomerase reverse transcriptase (hTERT) is expressed in >85% of tumors but not most normal cells. As a result, this antigen has received considerable attention from those interested cancer immunotherapy. Specifically, there been strong interest MHC class I-associated peptides derived hTERT because these are on the cell surface and thus may enable targeting tumor Much focused peptide 540-548, ILAKFLHWL, which was predicted to exhibit strongest binding common HLA A*0201...
Engineered T cells hold great promise to become part of an effective HIV cure strategy, but it is currently unclear how best redirect target HIV. To gain insight, we generated engineered using lentiviral vectors encoding one three distinct HIV-specific cell receptors (TCRs) or a previously optimized HIV-targeting chimeric antigen receptor (CAR) and compared their functional capabilities. All had robust, antigen-specific polyfunctional cytokine profiles when mixed with artificial...
Congenic mouse strains VM/Dk and VM-Sinc s7/Dk differ at the Sinc gene, which controls incubation period of scrapie in mice; mice are p7p7 s7s7. Restriction fragment length polymorphism DNA sequencing analysis demonstrated that PrP genes also these strains, confirming close genetic linkage PrP. Using restriction enzyme HhaI, we have shown least 100 kb flanking gene differs between two therefore congruence is still not certain.
Plasmid-encoded fusidic acid resistance in Escherichia coli is mediated by a common variant of chloramphenicol acetyltransferase (EC 2.3.1.28), an enzyme which effector resistance. Resistance to consequence acetylation the antibiotic catalysed and failure 3-acetoxy product bind bacterial ribosomes. Cell-free coupled transcription translation studies are agreement with genetic indicated that entire structural gene for type I necessary phenotype. The mechanism does not involve covalent...
Ninety‐two dual‐wage and 103 single‐wage Indian families with a preschool‐age child residing in extended nuclear households provided assessments regarding their beliefs about the division of household chores, financial responsibilities, childcare, filial obligations. Analysis focused on possible differences belief structures that may be attributed to gender parent, family structural living arrangement, maternal employment outside home. Husbands wives did not differ ideological any components...
Abstract Adoptive T cell therapy with cells expressing affinity-enhanced TCRs has shown promising results in phase 1/2 clinical trials for solid and hematological tumors. However, depth durability of responses to adoptive can suffer from an inhibitory tumor microenvironment. A common immune-suppressive agent is TGF-β, which secreted by recruited the tumor. We investigated whether human could be engineered resistant inhibition TGF-β. Truncating intracellular signaling domain TGF-β receptor...
Certain polysulphated polyanions have been shown to prophylactic effects on the progression of transmissible spongiform encephalopathy disease, presumably because they bind prion protein (PrP). Until now, difficulty obtaining large quantities native PrP has precluded detailed studies these interactions. We over-expressed murine recombinant (recPrP), lacking its glycophosphoinositol membrane anchor, in modified mammalian cells. Milligram secreted, soluble and partially glycosylated were...