Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313373585> ?p ?o ?g. }
Showing items 1 to 78 of
78
with 100 items per page.
- W4313373585 endingPage "241.19" @default.
- W4313373585 startingPage "241.19" @default.
- W4313373585 abstract "Abstract The therapeutic scope of MEK inhibitors (MEKis) is currently limited to use in BRAF mutant melanoma. Therefore, we aim to develop new strategies to extend their usage to MEKi resistant RAS mutant cancers, which represent an unmet clinical need. A strategy we investigated is to balance the positive and negative immunomodulatory effects of MEKis for optimal combination with immunotherapy. In Ras mutant murine lung cancers, CH5126766 (CKI27) is novel due to its ability to inhibit both RAF and MEK, preventing the rebound of ERK that normally results from the relief of negative feedback in the MAPK pathway. We observed that CKI27 increased MHC expression on tumor cells and T cell mediated killing. Yet, CKI27 also decreased T cell proliferation, activation, and cytolytic activity. Implementing a break for T cells to recover with intermittent dosing of CKI27 partially relieved these inhibitory effects. Further combination with co-stimulatory agonist antibodies targeting OX40 and GITR completely alleviated these T cell toxicities and increased combination efficacy with checkpoint blockade antibody anti-CTLA-4. Understanding the immunomodulatory effects of combining CKI27 with immunotherapy will elucidate the mechanism behind their increased efficacy. This will allow us to make more informed decisions in dosing regimens, overcoming resistance, and generating long-term immune responses in current and future clinical trials treating patients with RAS mutant cancers." @default.
- W4313373585 created "2023-01-06" @default.
- W4313373585 creator A5002951130 @default.
- W4313373585 creator A5007072019 @default.
- W4313373585 creator A5047591825 @default.
- W4313373585 creator A5054656505 @default.
- W4313373585 creator A5059172509 @default.
- W4313373585 creator A5060228803 @default.
- W4313373585 creator A5062466068 @default.
- W4313373585 creator A5082626339 @default.
- W4313373585 date "2020-05-01" @default.
- W4313373585 modified "2023-09-27" @default.
- W4313373585 title "Combining a novel dual RAF/MEK inhibitor with immunomodulation to promote an anti-tumor response" @default.
- W4313373585 doi "https://doi.org/10.4049/jimmunol.204.supp.241.19" @default.
- W4313373585 hasPublicationYear "2020" @default.
- W4313373585 type Work @default.
- W4313373585 citedByCount "0" @default.
- W4313373585 crossrefType "journal-article" @default.
- W4313373585 hasAuthorship W4313373585A5002951130 @default.
- W4313373585 hasAuthorship W4313373585A5007072019 @default.
- W4313373585 hasAuthorship W4313373585A5047591825 @default.
- W4313373585 hasAuthorship W4313373585A5054656505 @default.
- W4313373585 hasAuthorship W4313373585A5059172509 @default.
- W4313373585 hasAuthorship W4313373585A5060228803 @default.
- W4313373585 hasAuthorship W4313373585A5062466068 @default.
- W4313373585 hasAuthorship W4313373585A5082626339 @default.
- W4313373585 hasConcept C126322002 @default.
- W4313373585 hasConcept C170493617 @default.
- W4313373585 hasConcept C184235292 @default.
- W4313373585 hasConcept C203014093 @default.
- W4313373585 hasConcept C2776090121 @default.
- W4313373585 hasConcept C2777658100 @default.
- W4313373585 hasConcept C2777701055 @default.
- W4313373585 hasConcept C2778468042 @default.
- W4313373585 hasConcept C2781249067 @default.
- W4313373585 hasConcept C502942594 @default.
- W4313373585 hasConcept C57074206 @default.
- W4313373585 hasConcept C71924100 @default.
- W4313373585 hasConcept C86803240 @default.
- W4313373585 hasConcept C8891405 @default.
- W4313373585 hasConcept C95444343 @default.
- W4313373585 hasConcept C98274493 @default.
- W4313373585 hasConceptScore W4313373585C126322002 @default.
- W4313373585 hasConceptScore W4313373585C170493617 @default.
- W4313373585 hasConceptScore W4313373585C184235292 @default.
- W4313373585 hasConceptScore W4313373585C203014093 @default.
- W4313373585 hasConceptScore W4313373585C2776090121 @default.
- W4313373585 hasConceptScore W4313373585C2777658100 @default.
- W4313373585 hasConceptScore W4313373585C2777701055 @default.
- W4313373585 hasConceptScore W4313373585C2778468042 @default.
- W4313373585 hasConceptScore W4313373585C2781249067 @default.
- W4313373585 hasConceptScore W4313373585C502942594 @default.
- W4313373585 hasConceptScore W4313373585C57074206 @default.
- W4313373585 hasConceptScore W4313373585C71924100 @default.
- W4313373585 hasConceptScore W4313373585C86803240 @default.
- W4313373585 hasConceptScore W4313373585C8891405 @default.
- W4313373585 hasConceptScore W4313373585C95444343 @default.
- W4313373585 hasConceptScore W4313373585C98274493 @default.
- W4313373585 hasIssue "1_Supplement" @default.
- W4313373585 hasLocation W43133735851 @default.
- W4313373585 hasOpenAccess W4313373585 @default.
- W4313373585 hasPrimaryLocation W43133735851 @default.
- W4313373585 hasRelatedWork W2141202463 @default.
- W4313373585 hasRelatedWork W2164992866 @default.
- W4313373585 hasRelatedWork W2328771497 @default.
- W4313373585 hasRelatedWork W2401574182 @default.
- W4313373585 hasRelatedWork W2767735945 @default.
- W4313373585 hasRelatedWork W3045209127 @default.
- W4313373585 hasRelatedWork W3126366955 @default.
- W4313373585 hasRelatedWork W3200436128 @default.
- W4313373585 hasRelatedWork W4362493042 @default.
- W4313373585 hasRelatedWork W4362495258 @default.
- W4313373585 hasVolume "204" @default.
- W4313373585 isParatext "false" @default.
- W4313373585 isRetracted "false" @default.
- W4313373585 workType "article" @default.