FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308376048> ?p ?o ?g. }

• W4308376048 abstract "<h3>Background</h3> T-cell therapies have shown efficacy in numerous clinical settings. However, predictive biomarkers of response are lacking, and determining which T-cell therapy each cancer patient will respond to has been hindered by the absence of model systems that maintain the specific immunosuppressive features of each patient’s tumor microenvironment (TME). The Elephas live tumor fragment (LTF) platform is designed to enable prediction of clinical response to many types of immunotherapies, including cellular therapies and checkpoint blockade. The experiments described here examine T-cell activation, cytokine production, and tumor-cell killing following co-culture of LTFs with T-cell therapies. <h3>Methods</h3> Transgenic T-cells: LTFs were generated from two tumors that differ only by the presence or absence of a recombinantly expressed protein selectively recognized by targeted transgenic T cells. Transgenic and wildtype (WT) T-cells were isolated and co-cultured at 1:1, 5:1, and 10:1 T-cell:target-cell ratios using LTFs from both tumor types and assessed for T-cell activation and tumor cell viability using flow cytometry and cytokine/chemokine secretion profiling. TILs: Tumors were collected and processed for TIL expansion, which was conducted in the presence of IL-2 for 10 days. Following expansion, CD8 T-cells were isolated and co-cultured for 48h at a 1:1 ratio with LTFs from the same tumor. Tumor killing and T-cell activation were measured by flow cytometry. All animal studies were carried out in accordance with animal welfare guidelines and approved by the IACUC at Excelsior Labs. <h3>Results</h3> Transgenic T-cells: Flow cytometry revealed an increase in activation markers (CD25, CD69, ICOS, PD1, and CD137) on the surface of transgenic CD8 T-cells incubated with target-positive tumors, but not target-negative tumors, while WT T-cells displayed no increases when incubated with either tumor type. Secretome profiling demonstrated similar changes, with an increase in cytokine and chemokine secretion (IFNg, CXCL1, CCL4, and CXCL5) as the ratio of transgenic CD8 T-cells to target-cells increased, using target-positive, but not target-negative, LTFs. Decreases in tumor cell viability were also detected at higher T-cell:Target-cell ratios and were again only observed with target-positive LTFs. TILs: CD8 T-cells isolated from TILs, but not WT T-cells, that were co-cultured with LTFs demonstrated increased activation and resulted in a decrease in tumor cell number following 48h of culture. <h3>Conclusions</h3> We have verified target-specific transgenic T-cell activation, as well as reduced tumor viability in expanded TILs following co-culture with LTFs. These data lay the groundwork for future studies using the Elephas LTF platform to predict individual clinical responses to various T-cell therapies. <h3>Ethics Approval</h3> All animal studies were carried out in accordance with animal welfare guidelines and approved by the IACUC at Excelsior Labs." @default.
• W4308376048 created "2022-11-11" @default.
• W4308376048 creator A5003571412 @default.
• W4308376048 creator A5011128403 @default.
• W4308376048 creator A5016962224 @default.
• W4308376048 creator A5018384900 @default.
• W4308376048 creator A5024143109 @default.
• W4308376048 creator A5030626876 @default.
• W4308376048 creator A5030826096 @default.
• W4308376048 creator A5033555994 @default.
• W4308376048 creator A5038231951 @default.
• W4308376048 creator A5065531055 @default.
• W4308376048 creator A5068942560 @default.
• W4308376048 creator A5071363739 @default.
• W4308376048 creator A5077795264 @default.
• W4308376048 creator A5079394294 @default.
• W4308376048 creator A5079540618 @default.
• W4308376048 date "2022-11-01" @default.
• W4308376048 modified "2023-10-16" @default.
• W4308376048 title "187 A live tumor fragment platform suitable for assessing response to T-cell therapies" @default.
• W4308376048 doi "https://doi.org/10.1136/jitc-2022-sitc2022.0187" @default.
• W4308376048 hasPublicationYear "2022" @default.
• W4308376048 type Work @default.
• W4308376048 citedByCount "0" @default.
• W4308376048 crossrefType "proceedings-article" @default.
• W4308376048 hasAuthorship W4308376048A5003571412 @default.
• W4308376048 hasAuthorship W4308376048A5011128403 @default.
• W4308376048 hasAuthorship W4308376048A5016962224 @default.
• W4308376048 hasAuthorship W4308376048A5018384900 @default.
• W4308376048 hasAuthorship W4308376048A5024143109 @default.
• W4308376048 hasAuthorship W4308376048A5030626876 @default.
• W4308376048 hasAuthorship W4308376048A5030826096 @default.
• W4308376048 hasAuthorship W4308376048A5033555994 @default.
• W4308376048 hasAuthorship W4308376048A5038231951 @default.
• W4308376048 hasAuthorship W4308376048A5065531055 @default.
• W4308376048 hasAuthorship W4308376048A5068942560 @default.
• W4308376048 hasAuthorship W4308376048A5071363739 @default.
• W4308376048 hasAuthorship W4308376048A5077795264 @default.
• W4308376048 hasAuthorship W4308376048A5079394294 @default.
• W4308376048 hasAuthorship W4308376048A5079540618 @default.
• W4308376048 hasBestOaLocation W43083760481 @default.
• W4308376048 hasConcept C154317977 @default.
• W4308376048 hasConcept C167672396 @default.
• W4308376048 hasConcept C202751555 @default.
• W4308376048 hasConcept C203014093 @default.
• W4308376048 hasConcept C2776090121 @default.
• W4308376048 hasConcept C2776107976 @default.
• W4308376048 hasConcept C2777701055 @default.
• W4308376048 hasConcept C2778690821 @default.
• W4308376048 hasConcept C3020616263 @default.
• W4308376048 hasConcept C502942594 @default.
• W4308376048 hasConcept C553184892 @default.
• W4308376048 hasConcept C55493867 @default.
• W4308376048 hasConcept C71924100 @default.
• W4308376048 hasConcept C86803240 @default.
• W4308376048 hasConcept C8891405 @default.
• W4308376048 hasConceptScore W4308376048C154317977 @default.
• W4308376048 hasConceptScore W4308376048C167672396 @default.
• W4308376048 hasConceptScore W4308376048C202751555 @default.
• W4308376048 hasConceptScore W4308376048C203014093 @default.
• W4308376048 hasConceptScore W4308376048C2776090121 @default.
• W4308376048 hasConceptScore W4308376048C2776107976 @default.
• W4308376048 hasConceptScore W4308376048C2777701055 @default.
• W4308376048 hasConceptScore W4308376048C2778690821 @default.
• W4308376048 hasConceptScore W4308376048C3020616263 @default.
• W4308376048 hasConceptScore W4308376048C502942594 @default.
• W4308376048 hasConceptScore W4308376048C553184892 @default.
• W4308376048 hasConceptScore W4308376048C55493867 @default.
• W4308376048 hasConceptScore W4308376048C71924100 @default.
• W4308376048 hasConceptScore W4308376048C86803240 @default.
• W4308376048 hasConceptScore W4308376048C8891405 @default.
• W4308376048 hasLocation W43083760481 @default.
• W4308376048 hasOpenAccess W4308376048 @default.
• W4308376048 hasPrimaryLocation W43083760481 @default.
• W4308376048 hasRelatedWork W1568830440 @default.
• W4308376048 hasRelatedWork W2054101033 @default.
• W4308376048 hasRelatedWork W2055715607 @default.
• W4308376048 hasRelatedWork W2083635299 @default.
• W4308376048 hasRelatedWork W2912621681 @default.
• W4308376048 hasRelatedWork W3214468520 @default.
• W4308376048 hasRelatedWork W4242154564 @default.
• W4308376048 hasRelatedWork W4312075079 @default.
• W4308376048 hasRelatedWork W4317383376 @default.
• W4308376048 hasRelatedWork W4366590730 @default.
• W4308376048 isParatext "false" @default.
• W4308376048 isRetracted "false" @default.
• W4308376048 workType "article" @default.