FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385667672> ?p ?o ?g. }

• W4385667672 endingPage "e805462a" @default.
• W4385667672 startingPage "e805462a" @default.
• W4385667672 abstract "Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Cereblon E3 ligase modulator (CELMoD®) agents, including classic immunomodulatory (IMiD®) agents, have shown antitumor activity in MM. ALNUC is an asymmetric 2-arm, humanized IgG TCE that binds to BCMA and CD3ε in a 2 + 1 format. ALNUC mediates myeloma tumor cell killing by recruiting T cells to BCMA-expressing target cells, leading to immune synapse formation and T cell cytotoxic activity. Combining CELMoD agents with ALNUC may enhance antitumor activity. Aims: Evaluate the anti-MM potential of ALNUC+pomalidomide (POM) and novel CELMoD agents mezigdomide (MEZI) and iberdomide (IBER) in preclinical models. Methods: To evaluate effects of IMiD and CELMoD agents on ALNUC-mediated T cell anti-MM activity, healthy donor (HD) T cells and/or BCMA-expressing MM cell lines were pretreated with POM, MEZI, IBER, or DMSO for 16 h (T cells) or 72 h (MM cells) prior to co-culture; ALNUC was then added for 72 h and T cell activation and MM target cell depletion were measured. To evaluate IMiD and CELMoD agent effects on artificially exhausted T cells, HD CD3+ T cells were pretreated with anti-CD3/CD28 beads and POM, MEZI, IBER, or DMSO for 7 d prior to co-culture with MM cells and ALNUC. To determine if CELMoD treatment could reverse T cell dysfunction in patients (pts) with R/R MM, pretreatment PBMCs from pts with MM who had response (n=2) or nonresponse (n=3) to ALNUC in a phase 1 trial (NCT03486067) were co-cultured with H929 cells. Co-cultures were pretreated with MEZI 1 nM for 24 h prior to adding ALNUC. Flow cytometry was used to evaluate T cell proliferation and activation and MM cell apoptosis in all co-culture models. The effects of concurrent and sequential MEZI and ALNUC were studied in a humanized mouse H929 MM xenograft model. Results: In co-cultures with HD T cells, pretreatment of MM cells with MEZI, IBER, and POM increased ALNUC-induced tumor-cell killing potency and efficacy, resulting in IC50 decreases and greater reductions of MM cells across all cell lines vs ALNUC alone. ALNUC antitumor activity against the OPM-2 cell line was also enhanced by pre-treating T cells with MEZI and IBER, but not POM. Overall, MEZI showed the greatest enhancement of ALNUC-mediated activity in this in vitro model. In artificially exhausted HD T cells, enhanced antitumor activity was observed with MEZI and IBER, but not POM, vs DMSO. Based on the strong activity of MEZI in vitro, its ability to enhance ALNUC antitumor activity was tested in a humanized mouse MM xenograft model. Priming or concurrent treatment with MEZI enhanced T cell activation, promoted T cell infiltration of tumor tissue, and increased ALNUC-induced tumor clearance. The ability of MEZI to enhance ALNUC-mediated T-cell function was also examined in a co-culture model using MM pt-derived PBMCs harvested before ALNUC treatment. Pretreatment with MEZI increased ALNUC-mediated antitumor activity vs control in samples from both responder and nonresponder pts. Summary/Conclusion: The combination of ALNUC with novel CELMoD agents showed enhanced T cell mediated antitumor activity in both in vitro and ex vivo MM models. MEZI showed the greatest ability to enhance TCE-mediated antitumor activity while reversing artificial T cell dysfunction/exhaustion in vitro. Priming and concurrent treatment with MEZI enhanced ALNUC-induced T cell infiltration and activation in a MM xenograft model. The ability of MEZI to enhance ALNUC T cell antitumor function was confirmed using PBMCs from ALNUC monotherapy-treated pts with MM. These results provide a strong biological rationale for combining MEZI or IBER with ALNUC in the clinic to enhance responses in pts with MM. Keywords: Bispecific, Multiple myeloma, B-cell maturation antigen, Imids" @default.
• W4385667672 created "2023-08-09" @default.
• W4385667672 creator A5019098384 @default.
• W4385667672 creator A5019935868 @default.
• W4385667672 creator A5039907595 @default.
• W4385667672 creator A5057189669 @default.
• W4385667672 creator A5070175640 @default.
• W4385667672 creator A5070234110 @default.
• W4385667672 creator A5091104294 @default.
• W4385667672 date "2023-08-01" @default.
• W4385667672 modified "2023-09-27" @default.
• W4385667672 title "P799: SYNERGISTIC ANTITUMOR ACTIVITY OF THE BCMA 2 + 1 T CELL ENGAGER (TCE) ALNUCTAMAB (ALNUC; BMS-986349; CC-93269) AND CELMOD AGENTS IN MULTIPLE MYELOMA (MM) PRECLINICAL MODELS" @default.
• W4385667672 doi "https://doi.org/10.1097/01.hs9.0000970100.80546.2a" @default.
• W4385667672 hasPublicationYear "2023" @default.
• W4385667672 type Work @default.
• W4385667672 citedByCount "0" @default.
• W4385667672 crossrefType "journal-article" @default.
• W4385667672 hasAuthorship W4385667672A5019098384 @default.
• W4385667672 hasAuthorship W4385667672A5019935868 @default.
• W4385667672 hasAuthorship W4385667672A5039907595 @default.
• W4385667672 hasAuthorship W4385667672A5057189669 @default.
• W4385667672 hasAuthorship W4385667672A5070175640 @default.
• W4385667672 hasAuthorship W4385667672A5070234110 @default.
• W4385667672 hasAuthorship W4385667672A5091104294 @default.
• W4385667672 hasBestOaLocation W43856676721 @default.
• W4385667672 hasConcept C153911025 @default.
• W4385667672 hasConcept C154317977 @default.
• W4385667672 hasConcept C185592680 @default.
• W4385667672 hasConcept C202751555 @default.
• W4385667672 hasConcept C203014093 @default.
• W4385667672 hasConcept C2776090121 @default.
• W4385667672 hasConcept C2776364478 @default.
• W4385667672 hasConcept C2777478702 @default.
• W4385667672 hasConcept C2778524551 @default.
• W4385667672 hasConcept C502942594 @default.
• W4385667672 hasConcept C54355233 @default.
• W4385667672 hasConcept C55493867 @default.
• W4385667672 hasConcept C71924100 @default.
• W4385667672 hasConcept C81885089 @default.
• W4385667672 hasConcept C86803240 @default.
• W4385667672 hasConcept C8891405 @default.
• W4385667672 hasConcept C98274493 @default.
• W4385667672 hasConceptScore W4385667672C153911025 @default.
• W4385667672 hasConceptScore W4385667672C154317977 @default.
• W4385667672 hasConceptScore W4385667672C185592680 @default.
• W4385667672 hasConceptScore W4385667672C202751555 @default.
• W4385667672 hasConceptScore W4385667672C203014093 @default.
• W4385667672 hasConceptScore W4385667672C2776090121 @default.
• W4385667672 hasConceptScore W4385667672C2776364478 @default.
• W4385667672 hasConceptScore W4385667672C2777478702 @default.
• W4385667672 hasConceptScore W4385667672C2778524551 @default.
• W4385667672 hasConceptScore W4385667672C502942594 @default.
• W4385667672 hasConceptScore W4385667672C54355233 @default.
• W4385667672 hasConceptScore W4385667672C55493867 @default.
• W4385667672 hasConceptScore W4385667672C71924100 @default.
• W4385667672 hasConceptScore W4385667672C81885089 @default.
• W4385667672 hasConceptScore W4385667672C86803240 @default.
• W4385667672 hasConceptScore W4385667672C8891405 @default.
• W4385667672 hasConceptScore W4385667672C98274493 @default.
• W4385667672 hasIssue "S3" @default.
• W4385667672 hasLocation W43856676721 @default.
• W4385667672 hasLocation W43856676722 @default.
• W4385667672 hasOpenAccess W4385667672 @default.
• W4385667672 hasPrimaryLocation W43856676721 @default.
• W4385667672 hasRelatedWork W1522669222 @default.
• W4385667672 hasRelatedWork W1741438581 @default.
• W4385667672 hasRelatedWork W1991695056 @default.
• W4385667672 hasRelatedWork W2024305952 @default.
• W4385667672 hasRelatedWork W2055453275 @default.
• W4385667672 hasRelatedWork W2146775426 @default.
• W4385667672 hasRelatedWork W2322642253 @default.
• W4385667672 hasRelatedWork W2734396891 @default.
• W4385667672 hasRelatedWork W2890740159 @default.
• W4385667672 hasRelatedWork W2911664653 @default.
• W4385667672 hasVolume "7" @default.
• W4385667672 isParatext "false" @default.
• W4385667672 isRetracted "false" @default.
• W4385667672 workType "article" @default.