FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3177705124> ?p ?o ?g. }

• W3177705124 abstract "Clear cell renal cell carcinoma (ccRCC) is the major type of RCC and is among the 10 most common cancers in both men and women. Treatment of RCC has improved dramatically over the last decade, however, a curative treatment for advanced RCC remains rare. Chimeric Antigen Receptor (CAR) T cell therapy is a new type of “living drug”. The FDA approval of CAR-T cell therapies have ushered this new type of cellular immunotherapy into mainstream cancer therapy for hematologic malignancies. To date, these results have not been translatable to solid tumors due to inefficient homing of CAR-T cells, the immunosuppressive tumor microenvironment (TME), and on-target off-tumor toxicities due to shared antigens on normal tissues. Carbonic anhydrase IX (CAIX) is a therapeutic target against ccRCC that is under the control of HIF1α and becomes overexpressed on the surface of ccRCC cells because of VHL inactivation. The first anti-CAIX CAR-T study using the 1st generation G250-CD3 CAR-T cells plus IL-2 to treat patients with metastatic ccRCC was terminated due to hepatitis that developed after CAR-T cell infusions. The on-target off-tumor side effects were attributed to low expression of CAIX on healthy bile duct cells. To translate CAR-T cell therapy to ccRCC, we designed dual-targeted fine-tuned immune restoring (DFIR) CAR-T cells. The DFIR-CAR T cells secreted immune checkpoint inhibitor (ICI) monoclonal antibodies at the tumor site and exhibited superior efficacy and safety profiling. Increased efficacy is achieved through anti-CD70/CAIX dual-targeting CAR which allows the CAR-T cell activation in response to either antigen to mitigate solid tumor heterogeneity. Elevated safety is addressed through fine-tuned CARs which have the affinities of the scFv targeting moieties tailored so that they are activated only by high density tumor associated antigens (TAAs) but not the same antigens expressed at physiologic levels on normal tissues. The ICI payloads act globally on the TME, not only to prevent CAR-T cell exhaustion but also to restore anti-tumor activity of the educated tumor infiltrated lymphocytes (TILs) that have accumulated in the TME. In summary, our DFIR CAR-T cell therapy holds the promise to achieve cures of ccRCC by killing heterogenous ccRCC cells, mitigating against on-target off-tumor toxicity, reversing TME immunosuppression and restoring host anti-tumor immunity. We believe that DFIR-CAR T cells are ready to be translated to the clinic upon completion of pre-IND studies.Citation Format: Yufei Wang, Alicia Buck, Marion Grimaud, Sreekumar Kodangattil, Cecile Razimbaud, Atef Fayed, Matthew Chang, Aedin Culhane, David A. Braun, Toni K. Choueiri, Catherine J. Wu, Kevin S. Wei, Leo L. Chan, Brandon P. Piel, Elena V. Ivanova, Cloud P. Paweletz, David A. Barbie, Rebecca Jennings, Miriam Ficial, Maura Aliezah Sticco-Ivins, Sabina Signoretti, Gordon J. Freeman, Quan K. Zhu, Wayne A. Marasco. Development of dual-targeted fine-tuned immune restoring (DFIR) CAR T cell therapy for clear cell renal cell carcinoma (ccRCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 62." @default.
• W3177705124 created "2021-07-19" @default.
• W3177705124 creator A5000780125 @default.
• W3177705124 creator A5012020703 @default.
• W3177705124 creator A5025179355 @default.
• W3177705124 creator A5031849937 @default.
• W3177705124 creator A5033759527 @default.
• W3177705124 creator A5035182164 @default.
• W3177705124 creator A5035612745 @default.
• W3177705124 creator A5035644250 @default.
• W3177705124 creator A5046795494 @default.
• W3177705124 creator A5047701430 @default.
• W3177705124 creator A5048975003 @default.
• W3177705124 creator A5049557991 @default.
• W3177705124 creator A5049910071 @default.
• W3177705124 creator A5052504518 @default.
• W3177705124 creator A5055680400 @default.
• W3177705124 creator A5056573353 @default.
• W3177705124 creator A5060353514 @default.
• W3177705124 creator A5066563061 @default.
• W3177705124 creator A5069300441 @default.
• W3177705124 creator A5075310347 @default.
• W3177705124 creator A5076434834 @default.
• W3177705124 creator A5077525581 @default.
• W3177705124 creator A5078482949 @default.
• W3177705124 creator A5082180580 @default.
• W3177705124 date "2021-07-01" @default.
• W3177705124 modified "2023-10-15" @default.
• W3177705124 title "Abstract 62: Development of dual-targeted fine-tuned immune restoring (DFIR) CAR T cell therapy for clear cell renal cell carcinoma (ccRCC)" @default.
• W3177705124 doi "https://doi.org/10.1158/1538-7445.am2021-62" @default.
• W3177705124 hasPublicationYear "2021" @default.
• W3177705124 type Work @default.
• W3177705124 sameAs 3177705124 @default.
• W3177705124 citedByCount "0" @default.
• W3177705124 crossrefType "proceedings-article" @default.
• W3177705124 hasAuthorship W3177705124A5000780125 @default.
• W3177705124 hasAuthorship W3177705124A5012020703 @default.
• W3177705124 hasAuthorship W3177705124A5025179355 @default.
• W3177705124 hasAuthorship W3177705124A5031849937 @default.
• W3177705124 hasAuthorship W3177705124A5033759527 @default.
• W3177705124 hasAuthorship W3177705124A5035182164 @default.
• W3177705124 hasAuthorship W3177705124A5035612745 @default.
• W3177705124 hasAuthorship W3177705124A5035644250 @default.
• W3177705124 hasAuthorship W3177705124A5046795494 @default.
• W3177705124 hasAuthorship W3177705124A5047701430 @default.
• W3177705124 hasAuthorship W3177705124A5048975003 @default.
• W3177705124 hasAuthorship W3177705124A5049557991 @default.
• W3177705124 hasAuthorship W3177705124A5049910071 @default.
• W3177705124 hasAuthorship W3177705124A5052504518 @default.
• W3177705124 hasAuthorship W3177705124A5055680400 @default.
• W3177705124 hasAuthorship W3177705124A5056573353 @default.
• W3177705124 hasAuthorship W3177705124A5060353514 @default.
• W3177705124 hasAuthorship W3177705124A5066563061 @default.
• W3177705124 hasAuthorship W3177705124A5069300441 @default.
• W3177705124 hasAuthorship W3177705124A5075310347 @default.
• W3177705124 hasAuthorship W3177705124A5076434834 @default.
• W3177705124 hasAuthorship W3177705124A5077525581 @default.
• W3177705124 hasAuthorship W3177705124A5078482949 @default.
• W3177705124 hasAuthorship W3177705124A5082180580 @default.
• W3177705124 hasConcept C10882517 @default.
• W3177705124 hasConcept C121608353 @default.
• W3177705124 hasConcept C126322002 @default.
• W3177705124 hasConcept C1491633281 @default.
• W3177705124 hasConcept C203014093 @default.
• W3177705124 hasConcept C2776090121 @default.
• W3177705124 hasConcept C2776107976 @default.
• W3177705124 hasConcept C2777472916 @default.
• W3177705124 hasConcept C2777701055 @default.
• W3177705124 hasConcept C2781230642 @default.
• W3177705124 hasConcept C2781278892 @default.
• W3177705124 hasConcept C3875195 @default.
• W3177705124 hasConcept C502942594 @default.
• W3177705124 hasConcept C54355233 @default.
• W3177705124 hasConcept C71924100 @default.
• W3177705124 hasConcept C86803240 @default.
• W3177705124 hasConcept C8891405 @default.
• W3177705124 hasConceptScore W3177705124C10882517 @default.
• W3177705124 hasConceptScore W3177705124C121608353 @default.
• W3177705124 hasConceptScore W3177705124C126322002 @default.
• W3177705124 hasConceptScore W3177705124C1491633281 @default.
• W3177705124 hasConceptScore W3177705124C203014093 @default.
• W3177705124 hasConceptScore W3177705124C2776090121 @default.
• W3177705124 hasConceptScore W3177705124C2776107976 @default.
• W3177705124 hasConceptScore W3177705124C2777472916 @default.
• W3177705124 hasConceptScore W3177705124C2777701055 @default.
• W3177705124 hasConceptScore W3177705124C2781230642 @default.
• W3177705124 hasConceptScore W3177705124C2781278892 @default.
• W3177705124 hasConceptScore W3177705124C3875195 @default.
• W3177705124 hasConceptScore W3177705124C502942594 @default.
• W3177705124 hasConceptScore W3177705124C54355233 @default.
• W3177705124 hasConceptScore W3177705124C71924100 @default.
• W3177705124 hasConceptScore W3177705124C86803240 @default.
• W3177705124 hasConceptScore W3177705124C8891405 @default.
• W3177705124 hasLocation W31777051241 @default.
• W3177705124 hasOpenAccess W3177705124 @default.
• W3177705124 hasPrimaryLocation W31777051241 @default.
• W3177705124 hasRelatedWork W2916895208 @default.
• W3177705124 hasRelatedWork W2921642542 @default.
• W3177705124 hasRelatedWork W3024178724 @default.
• W3177705124 hasRelatedWork W3046189784 @default.

• next