Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313365639> ?p ?o ?g. }
Showing items 1 to 76 of
76
with 100 items per page.
- W4313365639 endingPage "136.14" @default.
- W4313365639 startingPage "136.14" @default.
- W4313365639 abstract "Abstract αPD-L1 is an FDA-approved bladder cancer (BC) immunotherapy but is effective in ≤30% of cases. We tested conjugates of αIL-2 antibody + IL-2 (IL-2c) that block IL-2 from binding high-affinity IL-2Rα (CD25) for preferential IL-2Rβ(CD122) binding. CD25 and CD122 are preferred for IL-2 capture by regulatory T cells and anti-tumor effector T cells (Teff), respectively, allowing IL-2c to target Teff preferentially. Orthotopic, intravesical (in bladder) MB49 BC produces PD-L1+BC tumors in syngeneic BL6 mice. αPD-L1 or IL-2c treated intravesical, but not lung metastatic MB49 produced by intravenous injection. Still, in metastatic BC, αPD-L1 + IL-2c (combo) reduced lung metastases and extended survival. Preliminary data found combo treatment efficacy was better in lung versus bladder. In subcutaneous (SQ) B16 melanoma, combo was better than single agents, and increased CD8+CXCR5+TCF-1+Tim-3−PD-1+T stem cells (CXCR5+SC, see X. Zhang poster) vs. single agents. Neither αPD-L1 nor combo increased CXCR5+SC in MB49 in bladder or lung metastases, suggesting a novel treatment mechanism. To test the impact of tumor PD-L1 on treatment efficacy, we made PD-L1KOMB49, but it did not grow in bladder or SQ in wild type mice, but grew similar to control MB49 in immunodeficient NSG mice SQ, suggesting tumor PD-L1 microenvironment-specific effects. PD-L1KOB16 grew well SQ in wild type mice, excluding a PD-L1-specific defect. Thus, tumor PD-L1 differs in immune evasion in a tumor-dependent manner. Selective IL-2 targeting to CD122 improves αPD-L1 treatment of metastatic BC. Mechanisms differ from melanoma, which could be due to tumor, PD-L1, or microenvironment effects. We are assessing mechanisms and αPD-1 treatment effects (also FDA-approved for BC)." @default.
- W4313365639 created "2023-01-06" @default.
- W4313365639 creator A5006310989 @default.
- W4313365639 creator A5016811631 @default.
- W4313365639 creator A5016862998 @default.
- W4313365639 creator A5017130108 @default.
- W4313365639 creator A5018112668 @default.
- W4313365639 creator A5022227961 @default.
- W4313365639 creator A5074770263 @default.
- W4313365639 creator A5079119716 @default.
- W4313365639 date "2019-05-01" @default.
- W4313365639 modified "2023-09-26" @default.
- W4313365639 title "Selective IL-2 receptor β (CD122) targeting improves αPD-L1 immunotherapy in a metastatic bladder cancer model" @default.
- W4313365639 doi "https://doi.org/10.4049/jimmunol.202.supp.136.14" @default.
- W4313365639 hasPublicationYear "2019" @default.
- W4313365639 type Work @default.
- W4313365639 citedByCount "0" @default.
- W4313365639 crossrefType "journal-article" @default.
- W4313365639 hasAuthorship W4313365639A5006310989 @default.
- W4313365639 hasAuthorship W4313365639A5016811631 @default.
- W4313365639 hasAuthorship W4313365639A5016862998 @default.
- W4313365639 hasAuthorship W4313365639A5017130108 @default.
- W4313365639 hasAuthorship W4313365639A5018112668 @default.
- W4313365639 hasAuthorship W4313365639A5022227961 @default.
- W4313365639 hasAuthorship W4313365639A5074770263 @default.
- W4313365639 hasAuthorship W4313365639A5079119716 @default.
- W4313365639 hasConcept C121608353 @default.
- W4313365639 hasConcept C126322002 @default.
- W4313365639 hasConcept C167672396 @default.
- W4313365639 hasConcept C203014093 @default.
- W4313365639 hasConcept C2776090121 @default.
- W4313365639 hasConcept C2776107976 @default.
- W4313365639 hasConcept C2776256026 @default.
- W4313365639 hasConcept C2777701055 @default.
- W4313365639 hasConcept C2780352672 @default.
- W4313365639 hasConcept C2781053074 @default.
- W4313365639 hasConcept C3020616263 @default.
- W4313365639 hasConcept C502942594 @default.
- W4313365639 hasConcept C71924100 @default.
- W4313365639 hasConcept C79484868 @default.
- W4313365639 hasConcept C8891405 @default.
- W4313365639 hasConceptScore W4313365639C121608353 @default.
- W4313365639 hasConceptScore W4313365639C126322002 @default.
- W4313365639 hasConceptScore W4313365639C167672396 @default.
- W4313365639 hasConceptScore W4313365639C203014093 @default.
- W4313365639 hasConceptScore W4313365639C2776090121 @default.
- W4313365639 hasConceptScore W4313365639C2776107976 @default.
- W4313365639 hasConceptScore W4313365639C2776256026 @default.
- W4313365639 hasConceptScore W4313365639C2777701055 @default.
- W4313365639 hasConceptScore W4313365639C2780352672 @default.
- W4313365639 hasConceptScore W4313365639C2781053074 @default.
- W4313365639 hasConceptScore W4313365639C3020616263 @default.
- W4313365639 hasConceptScore W4313365639C502942594 @default.
- W4313365639 hasConceptScore W4313365639C71924100 @default.
- W4313365639 hasConceptScore W4313365639C79484868 @default.
- W4313365639 hasConceptScore W4313365639C8891405 @default.
- W4313365639 hasIssue "1_Supplement" @default.
- W4313365639 hasLocation W43133656391 @default.
- W4313365639 hasOpenAccess W4313365639 @default.
- W4313365639 hasPrimaryLocation W43133656391 @default.
- W4313365639 hasRelatedWork W2904909612 @default.
- W4313365639 hasRelatedWork W2908970744 @default.
- W4313365639 hasRelatedWork W2912621681 @default.
- W4313365639 hasRelatedWork W3039388108 @default.
- W4313365639 hasRelatedWork W3197243161 @default.
- W4313365639 hasRelatedWork W4291378227 @default.
- W4313365639 hasRelatedWork W4293194630 @default.
- W4313365639 hasRelatedWork W4317383376 @default.
- W4313365639 hasRelatedWork W4327715451 @default.
- W4313365639 hasRelatedWork W4366590730 @default.
- W4313365639 hasVolume "202" @default.
- W4313365639 isParatext "false" @default.
- W4313365639 isRetracted "false" @default.
- W4313365639 workType "article" @default.