FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308394515> ?p ?o ?g. }

• W4308394515 abstract "<h3>Background</h3> Despite recent advancements with immune checkpoint inhibitors (e.g., anti-PD1 inhibitors) many cancer patients develop treatment resistance, which supports the study of alternative approaches to induce potent and safe anti-tumor T cell responses. STAR0602 is a bifunctional antibody-fusion molecule that selectively activates and expands a sub-set of human aβ T cells expressing variable (V) b6 and b10 regions of the T cell receptor (TCR). STAR0602 simultaneously engages a novel, non-clonal mode of TCR activation with cytokine co-stimulation. <h3>Methods</h3> The prevalence of STAR0602-targeted Vb T cells in tumor-infiltrating lymphocytes (TILs) from human tumor tissues was investigated by flow cytometry and by interrogating TIL TCRseq data from a large cancer database. The effects of STAR0602 on T cells from healthy donors and cancer patients were assessed <i>in vitro</i> by flow cytometry and NanoString. Using high tumor mutational burden (TMB) and anti-PD1-insensitive murine and human models, we investigated anti-tumor activity, mechanism of action, and an enrichment strategy for patient trials. Finally, the pharmacokinetics (PK) and pharmacodynamics (PD) of IV STAR0602 were investigated in Cynomolgus monkeys. <h3>Results</h3> Presence of STAR0602-targeted Vb T cells were confirmed in tissue from a range of human tumors, and present as 10-12% of TILs. Stimulation of T cells with STAR0602 resulted in potent expansion with ~80% adopting a novel memory phenotype, and significant boosting of antigen-specific T cells. In human autologous tumor organoid models, STAR0602 induced potent expansion of TILs and killing of tumors, including several PD1 refractory tumors. Dose-related anti-tumor activity (100% cure rate with a murine surrogate (mSTAR0602)) in EMT6-bearing mice correlated with expansion of memory Vb CD8⁺ T cells. In Cynomolgus monkeys, IV STAR0602 induced robust expansion of Vb CD8⁺ T cells in blood, with limited cytokine release or expansion of Treg. These data were used to build a PK/PD model to simulate human pharmacology and design a first-in-human trial with an enriched patient population. <h3>Conclusions</h3> STAR0602 is a first-in-class T cell activator that targets subsets of the germline TCR repertoire that are enriched in TILs. STAR0602 potently expands both naive and antigen-specific human T cells. In PD1 refractory human and murine tumor models with a high TMB, STAR0602 and mSTAR0602 induce potent anti-tumor activity as monotherapy, mediated by selective expansion of Vb CD8⁺ memory T cells. This pharmacology was translated into monkeys with IV dosed STAR0602 and supports the design of a novel Phase 1/2 precision-oncology trial with STAR0602 planned to commence in 2022." @default.
• W4308394515 created "2022-11-11" @default.
• W4308394515 creator A5000204204 @default.
• W4308394515 creator A5002298571 @default.
• W4308394515 creator A5008479799 @default.
• W4308394515 creator A5020286464 @default.
• W4308394515 creator A5021609253 @default.
• W4308394515 creator A5032625177 @default.
• W4308394515 creator A5049548374 @default.
• W4308394515 creator A5052157883 @default.
• W4308394515 creator A5059931764 @default.
• W4308394515 creator A5070669850 @default.
• W4308394515 creator A5072971421 @default.
• W4308394515 creator A5082123157 @default.
• W4308394515 creator A5082268512 @default.
• W4308394515 date "2022-11-01" @default.
• W4308394515 modified "2023-09-25" @default.
• W4308394515 title "1337 Preclinical evaluation of STAR0602, a novel, first-in-class anti-TCR Vb targeted bispecific antibody with potent anti-tumor activity for PD-1 refractory solid tumors" @default.
• W4308394515 doi "https://doi.org/10.1136/jitc-2022-sitc2022.1337" @default.
• W4308394515 hasPublicationYear "2022" @default.
• W4308394515 type Work @default.
• W4308394515 citedByCount "0" @default.
• W4308394515 crossrefType "proceedings-article" @default.
• W4308394515 hasAuthorship W4308394515A5000204204 @default.
• W4308394515 hasAuthorship W4308394515A5002298571 @default.
• W4308394515 hasAuthorship W4308394515A5008479799 @default.
• W4308394515 hasAuthorship W4308394515A5020286464 @default.
• W4308394515 hasAuthorship W4308394515A5021609253 @default.
• W4308394515 hasAuthorship W4308394515A5032625177 @default.
• W4308394515 hasAuthorship W4308394515A5049548374 @default.
• W4308394515 hasAuthorship W4308394515A5052157883 @default.
• W4308394515 hasAuthorship W4308394515A5059931764 @default.
• W4308394515 hasAuthorship W4308394515A5070669850 @default.
• W4308394515 hasAuthorship W4308394515A5072971421 @default.
• W4308394515 hasAuthorship W4308394515A5082123157 @default.
• W4308394515 hasAuthorship W4308394515A5082268512 @default.
• W4308394515 hasBestOaLocation W43083945151 @default.
• W4308394515 hasConcept C147483822 @default.
• W4308394515 hasConcept C159654299 @default.
• W4308394515 hasConcept C19317047 @default.
• W4308394515 hasConcept C203014093 @default.
• W4308394515 hasConcept C2776090121 @default.
• W4308394515 hasConcept C2776662205 @default.
• W4308394515 hasConcept C2777701055 @default.
• W4308394515 hasConcept C2778326572 @default.
• W4308394515 hasConcept C502942594 @default.
• W4308394515 hasConcept C553184892 @default.
• W4308394515 hasConcept C71924100 @default.
• W4308394515 hasConcept C8891405 @default.
• W4308394515 hasConceptScore W4308394515C147483822 @default.
• W4308394515 hasConceptScore W4308394515C159654299 @default.
• W4308394515 hasConceptScore W4308394515C19317047 @default.
• W4308394515 hasConceptScore W4308394515C203014093 @default.
• W4308394515 hasConceptScore W4308394515C2776090121 @default.
• W4308394515 hasConceptScore W4308394515C2776662205 @default.
• W4308394515 hasConceptScore W4308394515C2777701055 @default.
• W4308394515 hasConceptScore W4308394515C2778326572 @default.
• W4308394515 hasConceptScore W4308394515C502942594 @default.
• W4308394515 hasConceptScore W4308394515C553184892 @default.
• W4308394515 hasConceptScore W4308394515C71924100 @default.
• W4308394515 hasConceptScore W4308394515C8891405 @default.
• W4308394515 hasLocation W43083945151 @default.
• W4308394515 hasOpenAccess W4308394515 @default.
• W4308394515 hasPrimaryLocation W43083945151 @default.
• W4308394515 hasRelatedWork W1484614058 @default.
• W4308394515 hasRelatedWork W1484759019 @default.
• W4308394515 hasRelatedWork W1972479046 @default.
• W4308394515 hasRelatedWork W2001055320 @default.
• W4308394515 hasRelatedWork W2031356189 @default.
• W4308394515 hasRelatedWork W2040191638 @default.
• W4308394515 hasRelatedWork W2150135081 @default.
• W4308394515 hasRelatedWork W2220102944 @default.
• W4308394515 hasRelatedWork W3048051248 @default.
• W4308394515 hasRelatedWork W4313376859 @default.
• W4308394515 isParatext "false" @default.
• W4308394515 isRetracted "false" @default.
• W4308394515 workType "article" @default.