Immunogenic Cell Death Traits Emitted from Chronic Lymphocytic Leukemia Cells Following Treatment with a Novel Anti-Cancer Agent, SpiD3
<b>Background:</b> Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line strategies. Moreover, immunotherapeutic s...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/12/2857 |
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| Summary: | <b>Background:</b> Targeted therapies (e.g., ibrutinib) have markedly improved chronic lymphocytic leukemia (CLL) management; however, ~20% of patients experience disease relapse, suggesting the inadequate depth and durability of these front-line strategies. Moreover, immunotherapeutic success in CLL has been stifled by its pro-tumor microenvironment milieu and low mutational burden, cultivating poor antigenicity and limited ability to generate anti-tumor immunity through adaptive immune cell engagement. Previously, we have demonstrated how a three-carbon-linker spirocyclic dimer (SpiD3) promotes futile activation of the unfolded protein response (UPR) in CLL cells through immense misfolded-protein mimicry, culminating in insurmountable ER stress and programmed CLL cell death. <b>Method:</b> Herein, we used flow cytometry and cell-based assays to capture the kinetics and magnitude of SpiD3-induced damage-associated molecular patterns (DAMPs) in CLL cell lines and primary samples. <b>Result:</b> SpiD3 treatment, <i>in vitro</i> and <i>in vivo</i>, demonstrated the capacity to propagate immunogenic cell death through emissions of classically immunogenic DAMPs (CALR, ATP, HMGB1) and establish a chemotactic gradient for bone marrow-derived dendritic cells. <b>Conclusions:</b> Thus, this study supports future investigation into the relationship between novel therapeutics, manners of cancer cell death, and their contributions to adaptive immune cell engagement as a means for improving anti-cancer therapy in CLL. |
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| ISSN: | 2227-9059 |