P1218: First-in-Human Study of Cd19/Bcma Dual-Targeting Fast Car-T Gc012f for Patients With Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma

Chen, X.; Ping, Yu; Li, L.; Zhang, L.; Zhang, X.; Huang, Jinsheng; Sersch, M.; Wang, Z.; Song, D.; Wang, H.; Shen, L.; Zhao, W.; Zhang, Huan-Bo; Zhang, M.; Zhang, Y.

doi:10.1097/01.hs9.0000847736.14020.3e

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as many CD19, CD20 and/or CD22 targeting CAR T cell products are currently under investigation and four different anti-CD19 CAR T cell products are already approved, the role of BCMA as target antigen for the treatment of B cell lymphoma is for now less clear compared to CD19. Nonetheless, CD19/BCMA dual-targeting CAR approaches have been already tested for relapsed/refractory B cell NHL [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative performance of scFv-based anti-BCMA CAR formats for improved T cell therapy in multiple myeloma

Stock,

Fertig,

Gottschlich

et al. 2024

Cancer Immunol Immunother

View full text Add to dashboard Cite

In multiple myeloma (MM), B cell maturation antigen (BCMA)-directed CAR T cells have emerged as a novel therapy with potential for long-term disease control. Anti-BCMA CAR T cells with a CD8-based transmembrane (TM) and CD137 (41BB) as intracellular costimulatory domain are in routine clinical use. As the CAR construct architecture can differentially impact performance and efficacy, the optimal construction of a BCMA-targeting CAR remains to be elucidated. Here, we hypothesized that varying the constituents of the CAR structure known to impact performance could shed light on how to improve established anti-BCMA CAR constructs. CD8TM.41BBIC-based anti-BCMA CAR vectors with either a long linker or a short linker between the light and heavy scFv chain, CD28TM.41BBIC-based and CD28TM.CD28IC-based anti-BCMA CAR vector systems were used in primary human T cells. MM cell lines were used as target cells. The short linker anti-BCMA CAR demonstrated higher cytokine production, whereas in vitro cytotoxicity, T cell differentiation upon activation and proliferation were superior for the CD28TM.CD28IC-based CAR. While CD28TM.CD28IC-based CAR T cells killed MM cells faster, the persistence of 41BBIC-based constructs was superior in vivo. While CD28 and 41BB costimulation come with different in vitro and in vivo advantages, this did not translate into a superior outcome for either tested model. In conclusion, this study showcases the need to study the influence of different CAR architectures based on an identical scFv individually. It indicates that current scFv-based anti-BCMA CAR with clinical utility may already be at their functional optimum regarding the known structural variations of the scFv linker.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparative performance of scFv-based anti-BCMA CAR formats for improved T cell therapy in multiple myeloma

Stock,

Fertig,

Gottschlich

et al. 2024

Cancer Immunol Immunother

View full text Add to dashboard Cite

show abstract

Updates on CAR T cell therapy in multiple myeloma

Nasiri,

Asaadi,

Mirzadeh

et al. 2024

Biomark Res

View full text Add to dashboard Cite

Multiple myeloma (MM) is a hematological cancer characterized by the abnormal proliferation of plasma cells. Initial treatments often include immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs). Despite salient progress in diagnosis and treatment, most MM patients typically have a median life expectancy of only four to five years after starting treatment. In recent developments, the success of chimeric antigen receptor (CAR) T-cells in treating B-cell malignancies exemplifies a new paradigm shift in advanced immunotherapy techniques with promising therapeutic outcomes. Ide-cel and cilta-cel stand as the only two FDA-approved BCMA-targeted CAR T-cells for MM patients, a recognition achieved despite extensive preclinical and clinical research efforts in this domain. Challenges remain regarding certain aspects of CAR T-cell manufacturing and administration processes, including the lack of accessibility and durability due to T-cell characteristics, along with expensive and time-consuming processes limiting health plan coverage. Moreover, MM features, such as tumor antigen heterogeneity, antigen presentation alterations, complex tumor microenvironments, and challenges in CAR-T trafficking, contribute to CAR T-cell exhaustion and subsequent therapy relapse or refractory status. Additionally, the occurrence of adverse events such as cytokine release syndrome, neurotoxicity, and on-target, off-tumor toxicities present obstacles to CAR T-cell therapies. Consequently, ongoing CAR T-cell trials are diligently addressing these challenges and barriers. In this review, we provide an overview of the effectiveness of currently available CAR T-cell treatments for MM, explore the primary resistance mechanisms to these treatments, suggest strategies for improving long-lasting remissions, and investigate the potential for combination therapies involving CAR T-cells.

show abstract

P1218: First-in-Human Study of Cd19/Bcma Dual-Targeting Fast Car-T Gc012f for Patients With Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma

Cited by 2 publications

References 0 publications

Comparative performance of scFv-based anti-BCMA CAR formats for improved T cell therapy in multiple myeloma

Comparative performance of scFv-based anti-BCMA CAR formats for improved T cell therapy in multiple myeloma

Updates on CAR T cell therapy in multiple myeloma

Contact Info

Product

Resources

About