P977: Bispecific Cs1-Bcma Car-T Cells Are Clinically Active in Relapsed or Refractory Multiple Myeloma

Li, C.; Wang, X.; Wu, Z.; Luo, Wenjing; Zhang, Y.; Du, Min; Lu, C.; Kou, Haiming; Kang, Yu; Xu, Jinghua; Huang, P.; Xiong, W.; Jian, Zheng; Deng, Jun; Hu, Yiqiang; Mei, Heng

doi:10.1097/01.hs9.0000846776.32793.6f

Cited by 2 publications

(3 citation statements)

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“…Therefore, it is necessary to mitigate the effect of CS1 expression on NK cells during CS1 CAR-T therapy. Previous research [26] acknowledged T-cell fratricides and constructed tandem CAR-T targeting CS1 and BCMA, effectively eliminating the fratricidal effects caused by CS1 expression on normal lymphocytes. Concerns regarding the CAR-T fratricide have been raised by several CAR-T manufacturing techniques [6,27], such as the production of CS1 CAR-T derived from lymphocytes with a negative CS1 phenotype and the removal of CS1 expressed on T cells before the CAR structure is introduced.…”

Section: Discussionmentioning

confidence: 99%

CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy

Li,

Wang,

et al. 2024

J. Cancer

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Treatment with elotuzumab alone has no discernible antitumor effect and progress in chimeric antigen receptor T cells (CAR-T) therapy targeting CS1 is relatively slow. A retrospective analysis was performed on 236 patients with multiple myeloma (MM) and 30 patients with other plasma cell dyscrasias (PCDs). CS1 expression in NK cells, lymphocytes, and monoclonal plasma cells was assessed using multiparameter flow cytometry. Furthermore, new explorations were undertaken regarding the antitumor applications of elotuzumab. Patients with MM had significantly higher CS1 expression levels in plasma cells than other patients with PCDs, with no significant differences between lymphocytes and NK cells. In both patients with MM and other PCDs, CS1 expression was significantly higher in plasma cells than in NK cells and lymphocytes. Univariate and multivariate analyses revealed a significant correlation between CS1 expression in plasma (r = 0.60; P < 0.001) and NK (r = 0.79; P < 0.001) cells. Factors such as cytogenetic abnormalities, disease progression, and survival were not associated with CS1 expression in NK cells. Moreover, this study showed that elotuzumab strongly increases the cytotoxicity of NK cells against non-plasma and plasma tumor cells independent of their CS1 expression level. This underscores the potential of elotuzumab in combination with NK cells as an effective therapeutic strategy against a broad spectrum of tumor types.

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Section: Discussionmentioning

confidence: 99%

CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy

Li,

Wang,

et al. 2024

J. Cancer

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“…Other antigens that have evaluated with BCMA for dual target CAR-T constructs include GPRC5D and SLAMF7. 100,101 CAR-natural killer (CAR-NK) cells and other immune effector cell types are also being explored as ways to extend cellular therapy and overcome resistance to T-cell-mediated immunity. 102,103 Allogeneic CAR-T production could provide the promise of "off-the-shelf"…”

Section: Future Directionsmentioning

confidence: 99%

“…Dual targeting of CD19 and BCMA with CAR‐T in order to exert effects on the primary myeloma clone as well as myeloma stem cells is another strategy that has been explored, 39,98,99 although it remains unclear if the addition of CD19 targeting will have more meaningful long‐term benefit. Other antigens that have evaluated with BCMA for dual target CAR‐T constructs include GPRC5D and SLAMF7 100,101 …”

Section: Future Directionsmentioning

confidence: 99%

Update on the current and future use of CAR‐T to treat multiple myeloma

Gahvari,

Brunner,

Schmidt

et al. 2023

European J of Haematology

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Chimeric antigen receptor T‐cell (CAR‐T) therapy has become an important intervention in the management of relapsed and relapsed/refractory multiple myeloma (MM). Currently, B‐cell maturation antigen (BCMA) is the most targeted surface protein due to its ubiquitous expression on plasma cells, with increasing expression of this essential transmembrane protein on malignant plasma cells as patients develop more advanced disease. This review will explore the earliest CAR‐T trials in myeloma, discuss important issues involved in CAR‐T manufacturing and processing, as well as review current clinical trials that led to the approval of the two commercially available CAR‐T products, Idecabtagene vicleucel and ciltacabtagene autoleucel. The most recent data from trials investigating the use of CAR‐T as an earlier line of therapy will be presented. Finally, the problem of relapses after CAR‐T will be presented, including several theories as to why CAR‐T therapies fail and possible clinical caveats. The next generation of MM‐specific CAR‐T will likely include new targets such as G‐protein‐coupled receptor class C, Group 5, member D (GPRC5D) and signaling lymphocyte activation molecular Family 7 (SLAMF7). The role of CAR‐T in the treatment of MM will undoubtedly increase exponentially in the next decade.

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P977: Bispecific Cs1-Bcma Car-T Cells Are Clinically Active in Relapsed or Refractory Multiple Myeloma

Cited by 2 publications

References 0 publications

CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy

CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy

Update on the current and future use of CAR‐T to treat multiple myeloma

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