Design, Characterization, and Evaluation of scFvCD133/rGelonin: A CD133-Targeting Recombinant Immunotoxin for Use in Combination with Photochemical Internalization

Olsen, Cathrine Elisabeth; Cheung, Lawrence H.; Weyergang, Anette; Berg, Kristian; Vallera, Daniel A.; Rosenblum, Michael G.; Selbo, Pål Kristian

doi:10.3390/jcm9010068

Cited by 19 publications

(14 citation statements)

References 52 publications

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“…By the way, it is worth mentioning that photochemical internalization is a special CSC targeting strategy though PDT does not play a major role in this approach. In photochemical internalization, PS are modified by CSC biomarkers (such as CD133, CD44, CSPG4, and EpCAM)[ 106 - 109 ] that are first anchored to the cell membrane and then are endocytosed into intracellular vesicles. Finally, the drugs carried into the cell are released through PDT.…”

Section: Impact Of Ros From Pdt On Cscsmentioning

confidence: 99%

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Zhang

Wang

et al. 2020

WJSC

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Photodynamic therapy (PDT) is an effective and promising cancer treatment. PDT directly generates reactive oxygen species (ROS) through photochemical reactions. This oxygen-dependent exogenous ROS has anti-cancer stem cell (CSC) effect. In addition, PDT may also increase ROS production by altering metabolism, endoplasmic reticulum stress, or potential of mitochondrial membrane. It is known that the half-life of ROS in PDT is short, with high reactivity and limited diffusion distance. Therefore, the main targeting position of PDT is often the subcellular localization of photosensitizers, which is helpful for us to explain how PDT affects CSC characteristics, including differentiation, self-renewal, apoptosis, autophagy, and immunogenicity. Broadly speaking, excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA, change mitochondrial permeability, activate unfolded protein response, autophagy, and CSC resting state. Therefore, understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis. In this article, we review the effects of two types of photochemical reactions on PDT, the metabolic processes, and the biological effects of ROS in different subcellular locations on CSCs.

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Section: Impact Of Ros From Pdt On Cscsmentioning

confidence: 99%

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Zhang

Wang

et al. 2020

WJSC

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“…The samples were blocked with 0.5 % BSA for 10 min on ice and incubated with the primary mAbs biotin-anti-human CD274 (B7-H1, PD-L1) (clone 29E.2A3, BioLegend, San Diego, CA, USA) or biotin anti-mouse CD274 (clone 10F.9G2, BioLegend) in 0.5 % BSA for 20 min on ice. The samples were washed with PBS once and further incubated with streptavidin-AlexaFluor488 (BioLegend) in 0.5 % BSA for 20 min on ice, washed, and immediately analyzed on a flow cytometer LSRII (Becton Dickinson, Franklin Lakes, NJ, USA) as previously described [35]. Data were processed using the FlowJo software version 10.7.1 (Treestar, OR, USA).…”

Section: Methodsmentioning

confidence: 99%

Light-controlled elimination of PD-L1+ cells

Wong

Selbo

2021

Preprint

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The programmed death ligand-1 (PD-L1), also known as CD274 or B7-H1, is mainly expressed on cancer cells and/or immunosuppressive cells in the tumor microenvironment (TME) and plays an essential role in tumor progression and immune escape. Immune checkpoint inhibitors (ICIs) of the PD-1/PD-L1 axis have shown impressive clinical success, however, the majority of the patients do not respond to immune checkpoint therapy (ICT). Thus, to overcome ICT resistance there is a high need for potent and novel strategies that simultaneously target both tumor cells and immunosuppressive cells in the TME. In this study, we show that the intracellular light-controlled drug delivery method photochemical internalization (PCI) induce specific and strongly enhanced cytotoxic effects of the PD-L1-targeting immunotoxin, anti-PD-L1-saporin (Anti-PDL1-SAP), in the PD-L1+ triple-negative breast cancer MDA-MB-231 cell line, while no enhanced efficacy was obtained in the PD-L1 negative control cell line MDA-MB-453. Using fluorescence microscopy, we reveal that the anti-PD-L1 antibody binds to PD-L1 on the surface of the MDA-MD-231 cells and overnight accumulates in late endosomes and lysosomes where it co-localizes with the PCI photosensitizer fimaporfin (TPCS2a). Moreover, light-controlled endosomal/lysosomal escape of the anti-PD-L1 antibody and fimaporfin into the cytosol was obtained. We also confirm that the breast MDA-MB-468 and the prostate PC-3 and DU-145 cancer cell lines have subpopulations with PD-L1 expression. In addition, we show that interferon-gamma strongly induce PD-L1 expression in the per se PD-L1 negative CT26.WT cells and enhance the PD-L1 expression in MC-38 cells, of which both are murine colon cancer cell lines. In conclusion, our work provides an in vitro proof-of-concept of PCI-enhanced targeting and eradication of PD-L1 positive immunosuppressive cells. This light-controlled combinatorial strategy has a potential to advance cancer immunotherapy and should be explored in preclinical studies.

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“…to be resistant to chemotherapeutics, potent immunotoxins targeting CD133 are able to be internalized and kill tumor cells expressing CD133 [45][46][47] . Nevertheless, the potential for sender cells to target CD133 expressing receiver cells for cargo transfer has, to our knowledge, not been reported.…”

Section: Modular Design Of Csans Facilitates Use Of Single Chain Anti...mentioning

confidence: 99%

Macro-Chemical Biology: Engineering Biomimetic Trogocytosis with Farnesylated Chemically Self-Assembled Nanorings

Wang

Rozumalski

Lichtenfels

et al. 2022

Preprint

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With the recent success of cell-based therapies, there has been a rapidly emerging interest in the engineering of cell-cell interactions and communications. Inspired by the natural intercellular material transfer process of trans-endocytosis or trogocytosis, we proposed that targeted farnesylated chemically self-assembled nanorings (farnesyl-CSANs) could serve as a biomimetic trogocytosis vehicle for engineering directional cargo transfer between cells; thus, allowing cell-cell interactions to be monitored, as well as facilitating communication between the cells by delivery of bioactive species. The membranes of sender cells were stably modified by hydrophobic insertion with the targeted farnesyl-CSANs and to be efficiently transferred to receiver cells expressing the appropriate receptor by endocytosis. CSAN-assisted cell-cell cargo transfer (C4T) was demonstrated to be receptor-specific and dependent on direct cell-cell interactions, the rate of receptor internalization and the amount of receptor expression. In addition, C4T was shown to facilitate cell-to-cell delivery of an apoptosis inducing drug, as wells as antisense oligonucleotides (ASO). Taken together, the C4T approach is a potentially versatile biomimetic trogocytosis platform that can be used to monitor cell-cell interactions, as well as the engineering of cell-cell communications, such as cell-based drug delivery.

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Design, Characterization, and Evaluation of scFvCD133/rGelonin: A CD133-Targeting Recombinant Immunotoxin for Use in Combination with Photochemical Internalization

Cited by 19 publications

References 52 publications

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Light-controlled elimination of PD-L1+ cells

Macro-Chemical Biology: Engineering Biomimetic Trogocytosis with Farnesylated Chemically Self-Assembled Nanorings

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