Sabatolimab (<scp>MBG453</scp>) model‐informed drug development for dose selection in patients with myelodysplastic syndrome/acute myeloid leukemia and solid tumors

Xu, Simiao; Zhang, Na; Rinne, Mikael L.; Sun, Haiying; Stein, Andrew M.

doi:10.1002/psp4.12962

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…The suppression of TIM-3 is bringing new hope in the field of oncology: currently, Sabatolimab represents an innovative immunotherapeutic agent exhibiting immuno-myeloid activity, primarily by targeting the T-cell immunoglobulin domain and mucin domain-3 (TIM-3) on both immune cells and leukemic blasts. This agent is currently under investigation within the ambit of the STIMULUS clinical trial program, specifically for its potential efficacy in the treatment of various myeloid malignancies [ 109 , 110 ]. In the context of glioma, targeting TIM-3 has shown great results.…”

Section: Immuno-landscape Of Gliomas: Understanding the Immunological...mentioning

confidence: 99%

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Onciul,

Brehar,

Toader

et al. 2024

CIMB

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Gliomas constitute a diverse and complex array of tumors within the central nervous system (CNS), characterized by a wide range of prognostic outcomes and responses to therapeutic interventions. This literature review endeavors to conduct a thorough investigation of gliomas, with a particular emphasis on glioblastoma (GBM), beginning with their classification and epidemiological characteristics, evaluating their relative importance within the CNS tumor spectrum. We examine the immunological context of gliomas, unveiling the intricate immune environment and its ramifications for disease progression and therapeutic strategies. Moreover, we accentuate critical developments in understanding tumor behavior, focusing on recent research breakthroughs in treatment responses and the elucidation of cellular signaling pathways. Analyzing the most novel transcriptomic studies, we investigate the variations in gene expression patterns in glioma cells, assessing the prognostic and therapeutic implications of these genetic alterations. Furthermore, the role of epigenetic modifications in the pathogenesis of gliomas is underscored, suggesting that such changes are fundamental to tumor evolution and possible therapeutic advancements. In the end, this comparative oncological analysis situates GBM within the wider context of neoplasms, delineating both distinct and shared characteristics with other types of tumors.

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Section: Immuno-landscape Of Gliomas: Understanding the Immunological...mentioning

confidence: 99%

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Onciul,

Brehar,

Toader

et al. 2024

CIMB

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“…Sabatolimab is a first-in-class immuno-myeloid therapy that targets and inhibits the transmembrane protein TIM-3. This drug is a humanized monoclonal antibody (IgG4) and is still under clinical evaluation for the treatment of several immunogenic cancers [ 59 , 60 ].…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immunotherapy of Clear-Cell Renal-Cell Carcinoma

Grigolo,

Filgueira

2024

Cancers

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Clear-cell Renal-Cell Carcinoma (ccRCC) is the most common type of renal-cell carcinoma (RCC). In many cases, RCC patients manifest the first symptoms during the advanced stage of the disease. For this reason, immunotherapy appears to be one of the dominant treatments to achieve a resolution. In this review, we focus on the presentation of the main immune checkpoint proteins that act as negative regulators of immune responses, such as PD-1, CTLA-4, LAG-3, TIGIT, and TIM-3, and their respective inhibitors. Interleukin-2, another potential component of the treatment of ccRCC patients, has also been covered. The synergy between several immunotherapies is one of the main aspects that unites the conclusions of research in recent years. To date, the combination of several immunotherapies enhances the efficacy of a monotherapy, which often manifests important limitations. Immunotherapy aimed at restoring the anti-cancer immune response in ccRCC, involved in the recognition and elimination of cancer cells, may also be a valid solution for many other types of immunogenic tumors that are diagnosed in the final stages.

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“…TIM3 is a promising candidate for therapeutic intervention in AML and myelodysplastic syndrome. Sabatolimab targets the T-cell immunoglobulin domain and TIM-3 in LSCs [ 144 ]. Sabatolimab is suitable for the treatment of AML, myelodysplastic syndrome, and CML.…”

Section: Clinical Applications Of Lscsmentioning

confidence: 99%

Leukemic Stem Cells and Hematological Malignancies

Choi,

Kim,

Yoon

et al. 2024

IJMS

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The association between leukemic stem cells (LSCs) and leukemia development has been widely established in the context of genetic alterations, epigenetic pathways, and signaling pathway regulation. Hematopoietic stem cells are at the top of the bone marrow hierarchy and can self-renew and progressively generate blood and immune cells. The microenvironment, niche cells, and complex signaling pathways that regulate them acquire genetic mutations and epigenetic alterations due to aging, a chronic inflammatory environment, stress, and cancer, resulting in hematopoietic stem cell dysregulation and the production of abnormal blood and immune cells, leading to hematological malignancies and blood cancer. Cells that acquire these mutations grow at a faster rate than other cells and induce clone expansion. Excessive growth leads to the development of blood cancers. Standard therapy targets blast cells, which proliferate rapidly; however, LSCs that can induce disease recurrence remain after treatment, leading to recurrence and poor prognosis. To overcome these limitations, researchers have focused on the characteristics and signaling systems of LSCs and therapies that target them to block LSCs. This review aims to provide a comprehensive understanding of the types of hematopoietic malignancies, the characteristics of leukemic stem cells that cause them, the mechanisms by which these cells acquire chemotherapy resistance, and the therapies targeting these mechanisms.

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Sabatolimab (MBG453) model‐informed drug development for dose selection in patients with myelodysplastic syndrome/acute myeloid leukemia and solid tumors

Cited by 6 publications

References 43 publications

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Immunotherapy of Clear-Cell Renal-Cell Carcinoma

Leukemic Stem Cells and Hematological Malignancies

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