&lt;p&gt;Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment&lt;/p&gt;

Guo, Dan; Xu, Peipei; Chen, Dangui; Wang, Lili; Zhu, Yu; Zuo, Yifan; Chen, Bing

doi:10.2147/ijn.s233395

Cited by 16 publications

(9 citation statements)

References 30 publications

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“…The p53 signaling pathway is a recognized regulatory pathway related to cell apoptosis [2,29]. which can regulate the expression of apoptosis-related genes, such as Bax and Bcl-2, members of the Bcl-2 family [30]. The balance and protein-protein interactions between Bcl-2 family members is required to determine whether a cell undergoes cell survival or apoptosis.…”

Section: Discussionmentioning

confidence: 99%

IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis

Liao

Qin

et al. 2023

Preprint

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IKKα has been shown to be responsible of multiple pro-tumorigenic functions and therapy resistance independent of canonical NF-κB, but its role in acquired chemotherapy resistance in breast cancer remains unclarified. In this study, we obtained pre-treatment biopsy and post-treatment mastectomy specimens from aretrospective cohort of triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy(NAC) (n = 43). Immunohistochemical methods were used to detect the expression of IKKα before and after NAC, and the relationship between IKKα and the pathologic response to NAC was examined. In addition, we developed a new ADR-resistant MDA-MB-231 cell line(MDA-MB-231/ADR) and analyzed these cells for changes in IKKα expression, the role and mechanisms of the increased IKKα in promoting drug resistance were determined in vitro and in vivo. We demonstrated that the expression of IKKα in residual TNBC tissues after chemotherapy was significantly higher than that before chemotherapy, and was positively correlated with lower pathological reaction. IKKα expression was significantly higher in ADR-resistant TNBC cells than in ADR-sensitive cells, IKKα knockdown results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, IKKα knockdown promotes chemotherapeutic drug-induced tumor cell death in an transplanted tumor mouse model. Functionally, we demonstrated that IKKα knockdown significantly upregulated the expression of cleaved caspase 3 and Bax and inhibited the expression of Bcl-2 upon ADR treatment. Our findings highlighted that IKKα exerts an important and previously unknown role in promoting chemoresistance in TNBC, combining IKKα inhibition with chemotherapy may be an effective strategy to improve treatment outcome in chemoresistant TNBC patients.

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Section: Discussionmentioning

confidence: 99%

IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis

Liao

Qin

et al. 2023

Preprint

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“…Finally, two preclinical studies provide the rationale for potential novel strategies [ 92 , 93 ]. The first study demonstrated the possible safety and efficacy of AFM28, a novel bispecific innate cell engager (ICE ® ) targeting CD123 on MDS cells and CD16a on NK cells, with a higher stability compared with conventional Fc-optimized IgG1 antibodies [ 92 ].…”

Section: Target Immunotherapies In Mdsmentioning

confidence: 99%

“…The second study tested daunorubicin-loaded nanoparticles conjugated with anti-CD123 antibodies (DNR-CdTe-CD123) in MDS in vivo and in vitro models, proving the internalization of the complex promoted by the antibodies. Moreover, the carrier function fulfilled by the nanoparticles ensured a higher safety in vivo compared with unconjugated daunorubicin [ 93 ].…”

Section: Target Immunotherapies In Mdsmentioning

confidence: 99%

New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes

Gallazzi

Ucciero²,

Faraci³

et al. 2022

IJMS

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Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. These novel mAbs are currently under investigation for use as monotherapy or in combination with hypomethylating agents, BCL2 inhibitors, and chemotherapy in various clinical trials at different phases of development. Here, we review the main molecular targets and modes of action of novel mAb-based immunotherapies, which can represent the future of AML and higher risk MDS treatment.

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“…Most of them have shown good targeting and anti-tumor activity. For example, daunorubicin-loaded CdTe QDs conjugated to anti-CD123 mAbs (DNR-CdTe-CD123) treatment was designed for high-risk myelodysplastic syndromes (MDS) ( 106 ), the nanocomposite displayed higher inhibition rate and apoptosis rate in MDS cells than monotherapy, enhanced the therapeutic efficacy and reduced the side effects of daunorubicin. Genetically engineering cell-derived exosomes with anti-CD3 and anti-HER2 antibodies (aCD3-aHER2 SMART-Exos) dually target T cells and HER2 + breast cancer, selectively inducing HER2-expressing tumor-specific immunity and activating cytotoxic T cells toward attacking breast cancer cells ( 107 ).…”

Section: Applicable Systems Of Nanomodified Immunotherapymentioning

confidence: 99%

Anti-Cancer Nanomedicines: A Revolution of Tumor Immunotherapy

Peng

et al. 2020

Front. Immunol.

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Immunotherapies have been accelerating the development of anti-cancer clinical treatment, but its low objective responses and severe off-target immune-related adverse events (irAEs) limit the range of application. Strategies to remove these obstacles primarily focus on the combination of different therapies and the exploitation of new immunotherapeutic agents. Nanomedicine potentiates the effects of activating immune cells selectively and reversing tumor induced immune deficiency microenvironment through multiple mechanisms. In the last decade, a variety of nano-enabled tumor immunotherapies was under clinical investigation. As time goes by, the advantages of nanomedicine are increasingly prominent. With the continuous development of nanotechnology, nanomedicine will offer more distinctive perspectives in imaging diagnosis and treatment of tumors. In this Review, we wish to provide an overview of tumor immunotherapy and the mechanisms of nanomaterials that aim to enhance the efficacy of tumor immunotherapy under development or in clinic treatment.

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<p>Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment</p>

Cited by 16 publications

References 30 publications

IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis

IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis

New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes

Anti-Cancer Nanomedicines: A Revolution of Tumor Immunotherapy

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