Cell-Based Therapeutics: Making a Faustian Pact with Biology

Woodsworth, Daniel J.; Holt, Robert A.

doi:10.1016/j.molmed.2016.12.004

Cited by 10 publications

(12 citation statements)

References 65 publications

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“…To our knowledge, several preclinical models showed that MSCs can migrate into different types of tumors and therefore, this notion has inspired many experts in the field about the potential use of MSCs in anticancer drug/gene delivery [82,83]. In this regards, the genetically modified MSCs demonstrated a clear inhibition the proliferation of HCC in vitro and in vivo [84]. Delivering oncolytic viruses such as Measles virus into the tumor cells via MSCs represent another approach to avoid pre-existing immunity against the virus [85].…”

Section: Therapeutic Application Of Mscs In Liver Cancermentioning

confidence: 99%

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Elmahallawy

Mohamed

Abdo

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) is the most common hepatobiliary malignancy with limited therapeutic options. On the other hand, melatonin is an indoleamine that modulates a variety of potential therapeutic effects. In addition to its important role in the regulation of sleep–wake rhythms, several previous studies linked the biologic effects of melatonin to various substantial endocrine, neural, immune and antioxidant functions, among others. Furthermore, the effects of melatonin could be influenced through receptor dependent and receptor independent manner. Among the other numerous physiological and therapeutic effects of melatonin, controlling the survival and differentiation of mesenchymal stem cells (MSCs) has been recently discussed. Given its controversial interaction, several previous reports revealed the therapeutic potential of MSCs in controlling the hepatocellular carcinoma (HCC). Taken together, the intention of the present review is to highlight the effects of melatonin and mesenchymal stem cells as a key for functional integrity for liver cancer treatment. We hope to provide solid piece of information that may be helpful in designing novel drug targets to control HCC.

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Section: Therapeutic Application Of Mscs In Liver Cancermentioning

confidence: 99%

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Elmahallawy

Mohamed

Abdo

et al. 2020

IJMS

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“…Approval may be accelerated by knowledge of previous preclinical and clinical data on pharmacokinetics, side effects and regimens [5,87,88]. Anticancer activities of several anthelminthics attracted considerable interest, especially their capacity to target signal transduction pathways of CSCs/TICs of several tumor types.…”

Section: Resultsmentioning

confidence: 99%

Repurposing of Anthelminthics as Anticancer Drugs

Hamilton¹,

Rath²

2018

Oncomedicine

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“… 1 These efforts will rely heavily on the development of modules and systems that perform specific sensory, computational, and effector functions. 12 , 13 We report here our efforts to develop a cell-to-cell delivery module for cellular therapeutics by repurposing the granzyme-perforin pathway of cytotoxic lymphocytes. Our results support the use of granzyme B as a molecular chaperone for inserting protein payloads into this pathway and facilitating payload delivery to target cells.…”

Section: Discussionmentioning

confidence: 99%

“…These advances are a result of recombining the diverse functionality of biological systems to generate new functional biological molecules and pathways. 12 , 13 …”

Section: Introductionmentioning

confidence: 99%

Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway

Woodsworth¹,

Dreolini²,

Abraham³

et al. 2017

Molecular Therapy - Methods & Clinical Development

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There is great potential for engineering cellular therapeutics by repurposing biological systems. Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments. A synthetic chaperone consisting of the granzyme B ER signal peptide and a domain encompassing putative N-linked glycosylation sites in granzyme B is insufficient for payload transfer to target cells, whereas full-length granzyme B is sufficient for payload delivery. Combining our functional data with an analysis of the crystal structure of granzyme B suggests that the necessary motifs for granzyme B loading into lytic granules are dispersed throughout the primary amino acid sequence and are only functional when contiguous in the tertiary structure. These results illustrate that by using granzyme B as a molecular chaperone the granzyme-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies.

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Cell-Based Therapeutics: Making a Faustian Pact with Biology

Cited by 10 publications

References 65 publications

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Repurposing of Anthelminthics as Anticancer Drugs

Targeted Cell-to-Cell Delivery of Protein Payloads via the Granzyme-Perforin Pathway

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