FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4252003048> ?p ?o ?g. }

• W4252003048 endingPage "4092" @default.
• W4252003048 startingPage "4092" @default.
• W4252003048 abstract "Abstract Despite the impressive effects of checkpoint blockade antibody therapy seen across indications, many patients remain resistant to treatment. PD-1/PD-L1 blockade aims to restore the function of anergic tumor-infiltrating T cells, thereby inducing an efficient anti-tumor response. Thus, a prerequisite to benefit from checkpoint blockade is the presence of T cells in the tumor. One promising strategy to prime non-inflamed tumors for checkpoint blockade is the use of oncolytic viruses, which can additionally be engineered to express immunostimulatory molecules to further induce immune activation and T cell infiltration. In this study, we are investigating the use of the oncolytic adenovirus mLOAd703 expressing a murine trimerized membrane-bound (TMZ)-CD40L and 4-1BBL in the syngeneic murine B16 melanoma model. Adenoviruses cannot replicate in murine cells, but the immunostimulatory effect of the murine transgenes TMZ-CD40L and 4-1BBL can still be evaluated. LOAd703 (serotype 5/35) targets human CD46 for viral entry. Thus, a B16 cell line expressing human CD46 was used to allow infection. Upon infection with mLOAd703, B16-hCD46 cells not only expressed the transgenes TMZ-CD40L and 4-1BBL, but also changed their phenotype to become more immunogenic by upregulating co-stimulatory molecules CD80 and CD86, as well as MHC molecules. Moreover, expression of the death receptor Fas was increased, altogether potentially making the tumor cells more susceptible to T cell-mediated killing. Strikingly, two markers (CD44 and beta-3 integrin) associated with metastasis were reduced upon virus infection. Previous in vivo studies in immunocompetent C57BL6 mice with a predecessor of mLOAd703, which only expresses murine TMZ-CD40L, led to an increase of CD8+ T cells and CD11b+MHCII+ antigen presenting cells in the tumors. However, these cells also upregulated PD-1 or PD-L1, respectively, which warrants a combination with P-D1/PD-L1 checkpoint blockade. To evaluate this combination, mice with established B16-hCD46 tumors were treated with mLOAd703 (intratumoral 6x, 1x10e9 IU/mouse/injection), checkpoint blockade antibody (anti-mouse PD-1 or PD-L1, i.p. 6x 5mg/kg/mouse/injection; BioXcell), or treated in combination with mLOAd703 plus anti-PD-1 or mLOAd703 plus anti-PD-L1. Monotherapy with checkpoint blockade antibodies did not reduce tumor growth in this model. However, mLOAd703 reduced tumor growth as a monotherapy, but this reduction was even further enhanced in combination with both anti-PD-1 and anti-PD-L1 therapy. In conclusion, mLOAd703 could infect B16 cells expressing CD46, leading to TMZ-CD40L and 4-1BBL transgene expression. In addition, infected tumor cells became more immunogenic and reduced molecules involved in metastasis. In vivo studies revealed that mLOAd703 therapy sensitized PD-1/PD-L1-resistant mice to checkpoint blockade therapy. Citation Format: Jessica Wenthe, Sedigheh Naseri, Ann-Charlotte Hellström, Emma Eriksson, Angelica Loskog. CD40L/4-1BBL virotherapy enhances efficacy of checkpoint blockade therapy in a resistant melanoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4092." @default.
• W4252003048 created "2022-05-12" @default.
• W4252003048 creator A5004426426 @default.
• W4252003048 creator A5008096974 @default.
• W4252003048 creator A5033476705 @default.
• W4252003048 creator A5063027590 @default.
• W4252003048 creator A5076515855 @default.
• W4252003048 date "2019-07-01" @default.
• W4252003048 modified "2023-09-27" @default.
• W4252003048 title "Abstract 4092: CD40L/4-1BBL virotherapy enhances efficacy of checkpoint blockade therapy in a resistant melanoma model" @default.
• W4252003048 doi "https://doi.org/10.1158/1538-7445.am2019-4092" @default.
• W4252003048 hasPublicationYear "2019" @default.
• W4252003048 type Work @default.
• W4252003048 citedByCount "0" @default.
• W4252003048 crossrefType "journal-article" @default.
• W4252003048 hasAuthorship W4252003048A5004426426 @default.
• W4252003048 hasAuthorship W4252003048A5008096974 @default.
• W4252003048 hasAuthorship W4252003048A5033476705 @default.
• W4252003048 hasAuthorship W4252003048A5063027590 @default.
• W4252003048 hasAuthorship W4252003048A5076515855 @default.
• W4252003048 hasConcept C154317977 @default.
• W4252003048 hasConcept C159047783 @default.
• W4252003048 hasConcept C170493617 @default.
• W4252003048 hasConcept C202751555 @default.
• W4252003048 hasConcept C203014093 @default.
• W4252003048 hasConcept C2776090121 @default.
• W4252003048 hasConcept C2777701055 @default.
• W4252003048 hasConcept C2778297628 @default.
• W4252003048 hasConcept C2778468042 @default.
• W4252003048 hasConcept C2780851360 @default.
• W4252003048 hasConcept C2781101188 @default.
• W4252003048 hasConcept C39347974 @default.
• W4252003048 hasConcept C502942594 @default.
• W4252003048 hasConcept C55493867 @default.
• W4252003048 hasConcept C82210918 @default.
• W4252003048 hasConcept C86803240 @default.
• W4252003048 hasConcept C8891405 @default.
• W4252003048 hasConceptScore W4252003048C154317977 @default.
• W4252003048 hasConceptScore W4252003048C159047783 @default.
• W4252003048 hasConceptScore W4252003048C170493617 @default.
• W4252003048 hasConceptScore W4252003048C202751555 @default.
• W4252003048 hasConceptScore W4252003048C203014093 @default.
• W4252003048 hasConceptScore W4252003048C2776090121 @default.
• W4252003048 hasConceptScore W4252003048C2777701055 @default.
• W4252003048 hasConceptScore W4252003048C2778297628 @default.
• W4252003048 hasConceptScore W4252003048C2778468042 @default.
• W4252003048 hasConceptScore W4252003048C2780851360 @default.
• W4252003048 hasConceptScore W4252003048C2781101188 @default.
• W4252003048 hasConceptScore W4252003048C39347974 @default.
• W4252003048 hasConceptScore W4252003048C502942594 @default.
• W4252003048 hasConceptScore W4252003048C55493867 @default.
• W4252003048 hasConceptScore W4252003048C82210918 @default.
• W4252003048 hasConceptScore W4252003048C86803240 @default.
• W4252003048 hasConceptScore W4252003048C8891405 @default.
• W4252003048 hasIssue "13_Supplement" @default.
• W4252003048 hasLocation W42520030481 @default.
• W4252003048 hasOpenAccess W4252003048 @default.
• W4252003048 hasPrimaryLocation W42520030481 @default.
• W4252003048 hasRelatedWork W1525590896 @default.
• W4252003048 hasRelatedWork W1590539394 @default.
• W4252003048 hasRelatedWork W188365280 @default.
• W4252003048 hasRelatedWork W2009025366 @default.
• W4252003048 hasRelatedWork W2028926231 @default.
• W4252003048 hasRelatedWork W2069335042 @default.
• W4252003048 hasRelatedWork W2113315096 @default.
• W4252003048 hasRelatedWork W2316779859 @default.
• W4252003048 hasRelatedWork W2417011131 @default.
• W4252003048 hasRelatedWork W2800980962 @default.
• W4252003048 hasVolume "79" @default.
• W4252003048 isParatext "false" @default.
• W4252003048 isRetracted "false" @default.
• W4252003048 workType "article" @default.