Trial watch: bispecific antibodies for the treatment of relapsed or refractory large B-cell lymphoma

Despite the great advancements in treatment strategies for hematological malignancies (HMs) over the years, their effective treatment remains challenging. Conventional treatment strategies are burdened with several serious drawbacks limiting their effectiveness and safety. Improved understanding of tumor immunobiology has provided novel anti-cancer strategies targeting selected immune response components. Currently, immunotherapy is counted as the fourth pillar of oncological treatment (together with surgery, chemo- and radiotherapy) and is becoming standard in the treatment regimen, alone or in combination therapy. Several categories of immunotherapies have been developed and are currently being assessed in clinical trials for the treatment of blood cancers, including immune checkpoint inhibitors, antigen-targeted antibodies, antibody–drug conjugates, tumor vaccines, and adoptive cell therapies. However, monoclonal antibodies (mAbs) and their derivatives have achieved the most notable clinical outcome so far. Since the approval of rituximab for treating B-cell malignancies, the availability of mAbs against tumor-specific surface molecules for clinical use has flourished. Antibody-based therapy has become one of the most successful strategies for immunotherapeutic cancer treatment in the last few decades, and many mAbs have already been introduced into standard treatment protocols for some hematologic malignancies. To further increase the efficacy of mAbs, they can be conjugated to radioisotopes or cytostatic drugs, so-called antibody–drug conjugates. Moreover, with the growing recognition of T-cell immunity’s role in cancer development, strategies aimed at enhancing T cell activation and inhibiting mechanisms that suppress T cell function are actively being developed. This review provides a comprehensive overview of the current status of immunotherapeutic strategies based on monoclonal antibodies and their derivatives, including antibody–drug conjugates, bispecific T-cell engagers, and checkpoint inhibitors, approved for the treatment of various HMs.

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Disulfidptosis: A Novel Prognostic Criterion and Potential Treatment Strategy for Diffuse Large B-Cell Lymphoma (DLBCL)

Wang,

Tsukamoto,

Hori

et al. 2024

IJMS

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Diffuse Large B-cell Lymphoma (DLBCL), with its intrinsic genetic and epigenetic heterogeneity, exhibits significantly variable clinical outcomes among patients treated with the current standard regimen. Disulfidptosis, a novel form of regulatory cell death triggered by disulfide stress, is characterized by the collapse of cytoskeleton proteins and F-actin due to intracellular accumulation of disulfides. We investigated the expression variations of disulfidptosis-related genes (DRGs) in DLBCL using two publicly available gene expression datasets. The initial analysis of DRGs in DLBCL (GSE12453) revealed differences in gene expression patterns between various normal B cells and DLBCL. Subsequent analysis (GSE31312) identified DRGs strongly associated with prognostic outcomes, revealing eight characteristic DRGs (CAPZB, DSTN, GYS1, IQGAP1, MYH9, NDUFA11, NDUFS1, OXSM). Based on these DRGs, DLBCL patients were stratified into three groups, indicating that (1) DRGs can predict prognosis, and (2) DRGs can help identify novel therapeutic candidates. This study underscores the significant role of DRGs in various biological processes within DLBCL. Assessing the risk scores of individual DRGs allows for more precise stratification of prognosis and treatment strategies for DLBCL patients, thereby enhancing the effectiveness of clinical practice.

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Trial watch: bispecific antibodies for the treatment of relapsed or refractory large B-cell lymphoma

Cited by 4 publications

References 70 publications

The landscape of T-cell engagers for the treatment of follicular lymphoma

The landscape of T-cell engagers for the treatment of follicular lymphoma

Antibody-Based Immunotherapies for the Treatment of Hematologic Malignancies

Disulfidptosis: A Novel Prognostic Criterion and Potential Treatment Strategy for Diffuse Large B-Cell Lymphoma (DLBCL)

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