FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308377071> ?p ?o ?g. }

• W4308377071 abstract "<h3>Background</h3> T cell receptors (TCRs) have the potential to recognize epitopes derived from both intracellular and cell surface antigens. This facilitates targeting a wide range of tumor antigen classes including overexpressed, differentiation and cancer-testis antigens as well as antigens derived from driver mutations, frameshift mutations, splice variants and human endogenous retroviral elements (HERV). Despite this array of potentially targetable shared antigens, TCR-based anti-tumor therapies have to date only focused on a very limited number of target epitopes. The discovery of clinically relevant TCRs has been challenging due to the limitations in novel tumor antigen discovery and low throughput TCR screening approaches in addition to the inherently low frequency of tumor-reactive T cells in tumor samples and in peripheral blood. <h3>Methods</h3> We employ our sensitive and high-throughput Deep Immunomics platform using a mass-cytometry-based multiplexed tetramer staining approach to screen and characterize CD8+ T cells in peripheral blood mononuclear cells (PBMC) for reactivity against >500 potential T cell targets per sample. Downstream single cell sequencing of identified tumor antigen-specific T cells enables a combined analysis of T cell phenotype, transcriptome, TCR specificity and TCR sequence. TCRs identified using this approach are transduced for expression in engineered Jurkat reporter cells and primary T cells and evaluated for activation and effector function, respectively. <h3>Results</h3> We have utilized this approach to discover novel TCRs targeting a diverse list of potential tumor epitopes. We identified a TCR recognizing an HLA-A*02-restricted epitope derived from an HERV that is reported to be expressed across many cancer types. In Jurkat reporter cells, this TCR is activated specifically in the presence of the same epitope initially used to identify this TCR, but also through a related epitope variant from the same HERV subfamily. Furthermore, we have identified multiple TCRs that recognize an epitope resulting from alternative splicing of the target antigen in multiple cancers with mutations in a specific splicing factor. Primary T cells expressing these transgenic tumor specific TCR candidates demonstrated killing activity when exposed to target cells presenting the specific cognate peptide. <h3>Conclusions</h3> Our Deep Immunomics platform allows us to identify, characterize, and confirm the activity of TCR candidates against novel and therapeutically relevant shared cancer antigens. These findings validate our discovery workflow leading to a portfolio of potential clinical candidates that are currently under preclinical development." @default.
• W4308377071 created "2022-11-11" @default.
• W4308377071 creator A5012261254 @default.
• W4308377071 creator A5016456932 @default.
• W4308377071 creator A5023531050 @default.
• W4308377071 creator A5031774992 @default.
• W4308377071 creator A5047841842 @default.
• W4308377071 creator A5047965950 @default.
• W4308377071 creator A5048348913 @default.
• W4308377071 creator A5051773922 @default.
• W4308377071 creator A5058597775 @default.
• W4308377071 creator A5068190054 @default.
• W4308377071 creator A5069790289 @default.
• W4308377071 creator A5070195374 @default.
• W4308377071 creator A5074339941 @default.
• W4308377071 creator A5077291229 @default.
• W4308377071 date "2022-11-01" @default.
• W4308377071 modified "2023-10-16" @default.
• W4308377071 title "292 Discovery and development of t cell receptors for adoptive t cell therapy against solid tumors" @default.
• W4308377071 doi "https://doi.org/10.1136/jitc-2022-sitc2022.0292" @default.
• W4308377071 hasPublicationYear "2022" @default.
• W4308377071 type Work @default.
• W4308377071 citedByCount "0" @default.
• W4308377071 crossrefType "proceedings-article" @default.
• W4308377071 hasAuthorship W4308377071A5012261254 @default.
• W4308377071 hasAuthorship W4308377071A5016456932 @default.
• W4308377071 hasAuthorship W4308377071A5023531050 @default.
• W4308377071 hasAuthorship W4308377071A5031774992 @default.
• W4308377071 hasAuthorship W4308377071A5047841842 @default.
• W4308377071 hasAuthorship W4308377071A5047965950 @default.
• W4308377071 hasAuthorship W4308377071A5048348913 @default.
• W4308377071 hasAuthorship W4308377071A5051773922 @default.
• W4308377071 hasAuthorship W4308377071A5058597775 @default.
• W4308377071 hasAuthorship W4308377071A5068190054 @default.
• W4308377071 hasAuthorship W4308377071A5069790289 @default.
• W4308377071 hasAuthorship W4308377071A5070195374 @default.
• W4308377071 hasAuthorship W4308377071A5074339941 @default.
• W4308377071 hasAuthorship W4308377071A5077291229 @default.
• W4308377071 hasBestOaLocation W43083770711 @default.
• W4308377071 hasConcept C147483822 @default.
• W4308377071 hasConcept C153911025 @default.
• W4308377071 hasConcept C179464577 @default.
• W4308377071 hasConcept C19317047 @default.
• W4308377071 hasConcept C195616568 @default.
• W4308377071 hasConcept C203014093 @default.
• W4308377071 hasConcept C2776090121 @default.
• W4308377071 hasConcept C86803240 @default.
• W4308377071 hasConcept C8840205 @default.
• W4308377071 hasConcept C8891405 @default.
• W4308377071 hasConcept C95444343 @default.
• W4308377071 hasConceptScore W4308377071C147483822 @default.
• W4308377071 hasConceptScore W4308377071C153911025 @default.
• W4308377071 hasConceptScore W4308377071C179464577 @default.
• W4308377071 hasConceptScore W4308377071C19317047 @default.
• W4308377071 hasConceptScore W4308377071C195616568 @default.
• W4308377071 hasConceptScore W4308377071C203014093 @default.
• W4308377071 hasConceptScore W4308377071C2776090121 @default.
• W4308377071 hasConceptScore W4308377071C86803240 @default.
• W4308377071 hasConceptScore W4308377071C8840205 @default.
• W4308377071 hasConceptScore W4308377071C8891405 @default.
• W4308377071 hasConceptScore W4308377071C95444343 @default.
• W4308377071 hasLocation W43083770711 @default.
• W4308377071 hasOpenAccess W4308377071 @default.
• W4308377071 hasPrimaryLocation W43083770711 @default.
• W4308377071 hasRelatedWork W1613939252 @default.
• W4308377071 hasRelatedWork W1814963495 @default.
• W4308377071 hasRelatedWork W1989424382 @default.
• W4308377071 hasRelatedWork W2082500583 @default.
• W4308377071 hasRelatedWork W2094563378 @default.
• W4308377071 hasRelatedWork W2125043176 @default.
• W4308377071 hasRelatedWork W3012355104 @default.
• W4308377071 hasRelatedWork W4285585571 @default.
• W4308377071 hasRelatedWork W4306155276 @default.
• W4308377071 hasRelatedWork W657328650 @default.
• W4308377071 isParatext "false" @default.
• W4308377071 isRetracted "false" @default.
• W4308377071 workType "article" @default.