Bispecific T‐cell engagers for treatment of multiple myeloma

Ravi, Gayathri; Costa, Luciano J.

doi:10.1002/ajh.26628

Cited by 26 publications

(14 citation statements)

References 63 publications

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“…At the beginning of this century, the average overall survival of MM patients was about 3 years, when the main therapeutic agents were bortezomib, lenalidomide and thalidomide ( 26 ). The subsequent application of treatments including daratumumab, chimeric antigen receptor T cells, autologous hematopoietic stem cell transplantation, and bispecific T-cell engagers has greatly improved the survival of MM patients ( 27 , 28 , 29 ). However, regardless of the improvement in treatment modalities, MM is still an incurable tumor and it is inevitable that patients will experience recurrence.…”

Section: Discussionmentioning

confidence: 99%

LAMP5 may promote MM progression by activating p38

Chen¹,

Ma²

2023

Pathol. Oncol. Res.

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Multiple myeloma (MM) is the second most common tumor of the hematologic system. MM remains incurable at this time. In this study, we used bioinformatics analysis to find key genes in the pathogenesis of MM. We first found that Lysosome associated membrane protein 5 (LAMP5) expression was sequentially increased in healthy donors (HD), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and newly diagnosed MM (NDMM), relapsed MM (RMM). We collected bone marrow from patients with NDMM, HD and post-treatment MM (PTMM) and performed qPCR analysis of LAMP5, and found that the expression of LAMP5 is stronger in NDMM than in HD, and decreases after treatment. Western blotting assay also found more expression of LAMP5 in NDMM than in HD. Patients with high LAMP5 expression have a higher DS (Durie-Salmon) stage and worse prognosis. We next verified the expression of LAMP5 in four MM cell lines and silenced LAMP5 expression in RPMI-8226 and AMO-1, and explored the effects of LAMP5 silencing on MM cell apoptosis and cell cycle by flow cytometry and western blotting. Knockdown of LAMP5 promoted apoptosis in MM cells, but had no effect on the cell cycle. Mechanistically, LAMP5 may exert its pro-tumor effects in MM in part through activation of p38 protein. We screened LAMP5 for the first time as a key gene for MM progression and recurrence, and found that LAMP5 may exert its pro-tumor effects in MM through activation of p38 protein.

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Section: Discussionmentioning

confidence: 99%

LAMP5 may promote MM progression by activating p38

Chen¹,

Ma²

2023

Pathol. Oncol. Res.

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“…The two common antigens involved are CD3 and CD16, and BCMA is the target of MM plasma cells. Many studies with BITEs utilizing BCMA showed great efficacy with moderate toxicity, such as CRS (cytokine release syndrome) and associated neurotoxicity syndrome (ICANS) [ 80 - 82 ] .…”

Section: Bcma-targeted Treatment In Multiple Myelomamentioning

confidence: 99%

Anti-BCMA novel therapies for multiple myeloma

2023

Cancer Drug Resist

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Recent advances in multiple myeloma therapy have increased the depth of response and ultimately survivals; however, the prognosis remains poor. The BCMA antigen is highly expressed in myeloma cells, thus representing a target for novel therapies. Several agents that target BCMA through different mechanisms, including bispecific T cell engagers drug conjugated to antibody and CAR-T cells, are now available or under development. Immunotherapies targeting BCMA have shown good results in efficacy and safety in multiple myeloma patients previously treated with several lines of therapy. This review will discuss the recent development of anti-BCMA targeted treatments in myeloma, with a special focus on currently available agents.

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“…Similar to CAR T-cells, the dual binding of TEC results in the activation of the endogenous immune cells triggering cytokine release surge [5]. Apart from BCMA, other molecular targets on PCs currently assessed include the GPRC5D and FcRH5 [14].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Toxicity Profile of Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapies in Multiple Myeloma: Pathogenesis, Prevention and Management

et al. 2023

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Multiple myeloma is the second-most common hematologic malignancy in adults worldwide. Despite ongoing advancement in therapeutic modalities, it remains an incurable disease with a 5-year survival rate of approximately 50%. The recent development and introduction of anti-BCMA immunotherapies into clinical practice, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, has radically shifted the treatment paradigm. However, despite the promising potential of these therapies for broader application, frequent and significant adverse effects have been reported, both in short- and in long-term settings, requiring increasing awareness and vigilance in treating team, close monitoring, and prompt interventions with a multidisciplinary approach. In this review, we will discuss the toxicities associated with CAR-T cell therapy and bispecific antibodies, specifically, focusing on results from major clinical studies and real-world observations. In addition, we will emphasize on effective strategies for prevention, monitoring and management, and provide expert recommendations.

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Bispecific T‐cell engagers for treatment of multiple myeloma

Cited by 26 publications

References 63 publications

LAMP5 may promote MM progression by activating p38

LAMP5 may promote MM progression by activating p38

Anti-BCMA novel therapies for multiple myeloma

Toxicity Profile of Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapies in Multiple Myeloma: Pathogenesis, Prevention and Management

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