Matches in SemOpenAlex for { <https://semopenalex.org/work/W2485490743> ?p ?o ?g. }
Showing items 1 to 80 of
80
with 100 items per page.
- W2485490743 abstract "Immune evasion is a hallmark feature of tumors as they employ various strategies to suppress the immune system9s ability to recognize and destroy cancer cells. T cell checkpoint inhibitors such as anti-PD1 and anti-CTLA-4 antibodies spearhead the immune response against a variety of tumors. Numerous studies suggest that the complex immunosuppressive milieux require the development of additional therapeutic agents to potentiate active drugs and thereby broaden the utility and increase the therapeutic indices of revolutionary immune-oncology treatment modalities. The presence of immunosuppressive regulatory T cells (Tregs) in tumors, keeping tumoricidal Teffector cells in check, signals poor prognosis. Thus, depletion of Tregs or impairment of Treg function is an attractive therapeutic approach for cancer. USP7, a deubiquitylase enzyme implicated as a critical node in several cancer signaling pathways, has recently emerged as an essential factor in maintaining Treg functions. Progenra identified small molecule USP7 inhibitors and employed them to show that Treg specific inhibition of USP7 results in impairment of Treg function leading to immune activation, commensurate with the ablation of Foxp3, a transcription factor that is a target of USP7 and is essential to Treg activation. This USP7 inhibitor class was subsequently lead optimized, and selected USP7 inhibitors were evaluated in ADME/PK studies and shown to impair Treg functions and to exhibit powerful anti-tumor activity against syngeneic lung tumor models in immunocompetent mice. In addition, Progenra9s USP7 inhibitors significantly augmented the antitumor activity of anti-PD1 antibody, CAR T cell therapy, and cancer vaccines. These studies provide a strong rationale for the use of USP7 inhibitors in combination therapy protocols to improve the efficacy of currently approved cancer immunotherapy agents. Citation Format: Suresh Kumar, Jian Wu, Liquing Wang, Feng Wang, Matthew P. Kodrasov, Saket Agarwal, Ivan Sokirniy, Thomas Yeckley, Joseph Weinstock, Michael R. Mattern, Wayne W. Hancock. Small molecule T-reg inhibitors for cancer immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 559." @default.
- W2485490743 created "2016-08-23" @default.
- W2485490743 creator A5004185580 @default.
- W2485490743 creator A5005986044 @default.
- W2485490743 creator A5009921305 @default.
- W2485490743 creator A5037349330 @default.
- W2485490743 creator A5041975716 @default.
- W2485490743 creator A5046298813 @default.
- W2485490743 creator A5047555474 @default.
- W2485490743 creator A5063956079 @default.
- W2485490743 creator A5065622402 @default.
- W2485490743 creator A5075273343 @default.
- W2485490743 creator A5065416861 @default.
- W2485490743 date "2016-07-15" @default.
- W2485490743 modified "2023-09-25" @default.
- W2485490743 title "Abstract 559: Small molecule T-reg inhibitors for cancer immunotherapy" @default.
- W2485490743 doi "https://doi.org/10.1158/1538-7445.am2016-559" @default.
- W2485490743 hasPublicationYear "2016" @default.
- W2485490743 type Work @default.
- W2485490743 sameAs 2485490743 @default.
- W2485490743 citedByCount "0" @default.
- W2485490743 crossrefType "proceedings-article" @default.
- W2485490743 hasAuthorship W2485490743A5004185580 @default.
- W2485490743 hasAuthorship W2485490743A5005986044 @default.
- W2485490743 hasAuthorship W2485490743A5009921305 @default.
- W2485490743 hasAuthorship W2485490743A5037349330 @default.
- W2485490743 hasAuthorship W2485490743A5041975716 @default.
- W2485490743 hasAuthorship W2485490743A5046298813 @default.
- W2485490743 hasAuthorship W2485490743A5047555474 @default.
- W2485490743 hasAuthorship W2485490743A5063956079 @default.
- W2485490743 hasAuthorship W2485490743A5065416861 @default.
- W2485490743 hasAuthorship W2485490743A5065622402 @default.
- W2485490743 hasAuthorship W2485490743A5075273343 @default.
- W2485490743 hasConcept C121608353 @default.
- W2485490743 hasConcept C126322002 @default.
- W2485490743 hasConcept C159654299 @default.
- W2485490743 hasConcept C203014093 @default.
- W2485490743 hasConcept C2777701055 @default.
- W2485490743 hasConcept C2779727006 @default.
- W2485490743 hasConcept C2780674031 @default.
- W2485490743 hasConcept C502942594 @default.
- W2485490743 hasConcept C71924100 @default.
- W2485490743 hasConcept C8891405 @default.
- W2485490743 hasConceptScore W2485490743C121608353 @default.
- W2485490743 hasConceptScore W2485490743C126322002 @default.
- W2485490743 hasConceptScore W2485490743C159654299 @default.
- W2485490743 hasConceptScore W2485490743C203014093 @default.
- W2485490743 hasConceptScore W2485490743C2777701055 @default.
- W2485490743 hasConceptScore W2485490743C2779727006 @default.
- W2485490743 hasConceptScore W2485490743C2780674031 @default.
- W2485490743 hasConceptScore W2485490743C502942594 @default.
- W2485490743 hasConceptScore W2485490743C71924100 @default.
- W2485490743 hasConceptScore W2485490743C8891405 @default.
- W2485490743 hasLocation W24854907431 @default.
- W2485490743 hasOpenAccess W2485490743 @default.
- W2485490743 hasPrimaryLocation W24854907431 @default.
- W2485490743 hasRelatedWork W1987113274 @default.
- W2485490743 hasRelatedWork W2018730429 @default.
- W2485490743 hasRelatedWork W2020634893 @default.
- W2485490743 hasRelatedWork W2079940828 @default.
- W2485490743 hasRelatedWork W2277066200 @default.
- W2485490743 hasRelatedWork W2395721205 @default.
- W2485490743 hasRelatedWork W2401087683 @default.
- W2485490743 hasRelatedWork W2475647349 @default.
- W2485490743 hasRelatedWork W2479258345 @default.
- W2485490743 hasRelatedWork W2546726008 @default.
- W2485490743 hasRelatedWork W2547531492 @default.
- W2485490743 hasRelatedWork W2591654573 @default.
- W2485490743 hasRelatedWork W2625222005 @default.
- W2485490743 hasRelatedWork W2740597761 @default.
- W2485490743 hasRelatedWork W2782676239 @default.
- W2485490743 hasRelatedWork W2789350096 @default.
- W2485490743 hasRelatedWork W2885365017 @default.
- W2485490743 hasRelatedWork W2946683593 @default.
- W2485490743 hasRelatedWork W3091444202 @default.
- W2485490743 hasRelatedWork W3098454574 @default.
- W2485490743 isParatext "false" @default.
- W2485490743 isRetracted "false" @default.
- W2485490743 magId "2485490743" @default.
- W2485490743 workType "article" @default.