Bortezomib-resistant multiple myeloma patient-derived xenograft is sensitive to anti-CD47 therapy

Yue, Yanhua; Cao, Yang; Wang, Fei; Zhang, Naidong; Qi, Ziwei; Mao, Xunyuan; Guo, Shuxin; Li, Feng; Guo, Yanting; Lin, Yan; Dong, Weimin; Huang, Yuhui; Gu, Weiying

doi:10.1016/j.leukres.2022.106949

Cited by 3 publications

(3 citation statements)

References 49 publications

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“…Preclinical studies targeting CD47/SIRPα signaling pathway related immunotherapy has been explored in MM patients. Study demonstrated that bortezomib-resistant multiple myeloma patient-derived xenograft is sensitive to anti-CD47 therapy ( 77 ). Blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages showed phagocytosis and killing of MM cells in the 3D-tissue engineered bone marrow model ( 78 ).…”

Section: Targeting Cd47/sirpα Immunotherapy In Hematological Malignan...mentioning

confidence: 99%

Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

Jiang,

Sun,

Jiang

et al. 2024

Front. Oncol.

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Since its initial report in 2015, CD47 has garnered significant attention as an innate immune checkpoint, raising expectations to become the next “PD-1.” The optimistic early stages of clinical development spurred a flurry of licensing deals for CD47-targeted molecules and company mergers or acquisitions for related assets. However, a series of setbacks unfolded recently, starting with the July 2023 announcement of discontinuing the phase 3 ENHANCE study on Magrolimab plus Azacitidine for higher-risk myelodysplastic syndromes (MDS). Subsequently, in August 2023, the termination of the ASPEN-02 program, assessing Evorpacept in combination with Azacitidine in MDS patients, was disclosed due to insufficient improvement compared to Azacitidine alone. These setbacks have cast doubt on the feasibility of targeting CD47 in the industry. In this review, we delve into the challenges of developing CD47-SIRPα-targeted drugs, analyze factors contributing to the mentioned setbacks, discuss future perspectives, and explore potential solutions for enhancing CD47-SIRPα-targeted drug development.

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Section: Targeting Cd47/sirpα Immunotherapy In Hematological Malignan...mentioning

confidence: 99%

Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

Jiang,

Sun,

Jiang

et al. 2024

Front. Oncol.

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“…Recent studies reported that disrupting the CD47-TSP-1 interaction reduced angiogenesis in neuroblastoma and glioblastoma models, but selectively depleting CD47 in stromal cells increased angiogenesis and tumor burden in a syngeneic prostate cancer model [186,187]. Furthermore, inhibition of CD47 normalized tumor vasculature in a multiple myeloma model, which was associated with reduced expression of pro-angiogenic factors, increased expression of anti-angiogenic factors, and tumor growth inhibition [188]. Thus, the effects of TSP-1-CD47 interactions on angiogenesis may be malignancy-dependent, and further studies are needed to fully understand them.…”

Section: Cd47: Molecular Interactions Signaling Pathways and Malignan...mentioning

confidence: 99%

CD47: The Next Frontier in Immune Checkpoint Blockade for Non-Small Cell Lung Cancer

Lau,

Khavkine Binstock,

Thu

2023

Cancers

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The success of PD-1/PD-L1-targeted therapy in lung cancer has resulted in great enthusiasm for additional immunotherapies in development to elicit similar survival benefits, particularly in patients who do not respond to or are ineligible for PD-1 blockade. CD47 is an immunosuppressive molecule that binds SIRPα on antigen-presenting cells to regulate an innate immune checkpoint that blocks phagocytosis and subsequent activation of adaptive tumor immunity. In lung cancer, CD47 expression is associated with poor survival and tumors with EGFR mutations, which do not typically respond to PD-1 blockade. Given its prognostic relevance, its role in facilitating immune escape, and the number of agents currently in clinical development, CD47 blockade represents a promising next-generation immunotherapy for lung cancer. In this review, we briefly summarize how tumors disrupt the cancer immunity cycle to facilitate immune evasion and their exploitation of immune checkpoints like the CD47–SIRPα axis. We also discuss approved immune checkpoint inhibitors and strategies for targeting CD47 that are currently being investigated. Finally, we review the literature supporting CD47 as a promising immunotherapeutic target in lung cancer and offer our perspective on key obstacles that must be overcome to establish CD47 blockade as the next standard of care for lung cancer therapy.

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“…Li et al (47) found that anti-CD47 antibodies led to increased phagocytosis of glioma cells by macrophages and significantly reduced tumor growth rate in a mouse glioma model. Furthermore, anti-CD47 therapy has been shown to promote the polarization of TAMs from an M2-to an M1-like phenotype (48) and induce anti-tumor effects.…”

Section: Immunotherapeutic Strategies Targeting Immunosuppressive Cel...mentioning

confidence: 99%

The immunosuppressive microenvironment and immunotherapy in human glioblastoma

et al. 2022

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Glioblastoma multiforme (GBM) is the most malignant intracranial tumor in adults, characterized by extensive infiltrative growth, high vascularization, and resistance to multiple therapeutic approaches. Among the many factors affecting the therapeutic effect, the immunosuppressive GBM microenvironment that is created by cells and associated molecules via complex mechanisms plays a particularly important role in facilitating evasion of the tumor from the immune response. Accumulating evidence is also revealing a close association of the gut microbiota with the challenges in the treatment of GBM. The gut microbiota establishes a connection with the central nervous system through bidirectional signals of the gut–brain axis, thus affecting the occurrence and development of GBM. In this review, we discuss the key immunosuppressive components in the tumor microenvironment, along with the regulatory mechanism of the gut microbiota involved in immunity and metabolism in the GBM microenvironment. Lastly, we concentrate on the immunotherapeutic strategies currently under investigation, which hold promise to overcome the hurdles of the immunosuppressive tumor microenvironment and improve the therapeutic outcome for patients with GBM.

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Bortezomib-resistant multiple myeloma patient-derived xenograft is sensitive to anti-CD47 therapy

Cited by 3 publications

References 49 publications

Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

CD47: The Next Frontier in Immune Checkpoint Blockade for Non-Small Cell Lung Cancer

The immunosuppressive microenvironment and immunotherapy in human glioblastoma

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