A novel in vivo model using immunotoxin in the absence of p-glycoprotein to achieve ultra selective depletion of target cells: Applications in trogocytosis and beyond

Kathryn Brown; Lucy Meader; Anna Nowocin; Lindsey A. Edwards; Lawrence H. Cheung; Richard A. Smith; Michael G. Rosenblum; Wilson Wong

doi:10.1016/j.jim.2020.112794

A novel in vivo model using immunotoxin in the absence of p-glycoprotein to achieve ultra selective depletion of target cells: Applications in trogocytosis and beyond

Kathryn Brown, Lucy Meader, Anna Nowocin, Lindsey A. Edwards, Lawrence H. Cheung, Richard A. Smith, Michael G. Rosenblum, Wilson Wong^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

A commonly employed method to determine the function of a particular cell population and to assess its contribution to the overall system in vivo is to selectively deplete that population and observe the effects. Using monoclonal antibodies to deliver toxins to target cells can achieve this with a high degree of efficiency. Here, we describe an in vivo model combining the use of immunotoxins and multidrug resistant (MDR) gene deficient mice so that only MDR deficient cells expressing the target molecule would be depleted while target molecule expressing, but MDR sufficient, cells are spared. This allows targeted depletion at a higher degree of specificity than has been previously achieved. We have applied this technique to study trogocytosis, the intercellular transfer of cell surface molecules, but this principle could also be adapted using technology already available for use in other fields of study.

Original language	English
Article number	112794
Pages (from-to)	1-10
Journal	Journal of Immunological Methods
Volume	483
Early online date	16 May 2020
DOIs	https://doi.org/10.1016/j.jim.2020.112794
Publication status	Published - Aug 2020

Keywords

Antigen presentation
Cell depletion
Immunotoxin
Molecular transfer
Trogocytosis

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10.1016/j.jim.2020.112794

A novel in vivo_BROWN_Acc9May2020Epub16May2020_GREEN AAMAccepted author manuscript, 1.08 MBLicence: CC BY-NC-ND

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Brown, K., Meader, L., Nowocin, A., Edwards, L. A., Cheung, L. H., Smith, R. A., Rosenblum, M. G., & Wong, W. (2020). A novel in vivo model using immunotoxin in the absence of p-glycoprotein to achieve ultra selective depletion of target cells: Applications in trogocytosis and beyond. Journal of Immunological Methods, 483, 1-10. Article 112794. https://doi.org/10.1016/j.jim.2020.112794

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title = "A novel in vivo model using immunotoxin in the absence of p-glycoprotein to achieve ultra selective depletion of target cells: Applications in trogocytosis and beyond",

abstract = "A commonly employed method to determine the function of a particular cell population and to assess its contribution to the overall system in vivo is to selectively deplete that population and observe the effects. Using monoclonal antibodies to deliver toxins to target cells can achieve this with a high degree of efficiency. Here, we describe an in vivo model combining the use of immunotoxins and multidrug resistant (MDR) gene deficient mice so that only MDR deficient cells expressing the target molecule would be depleted while target molecule expressing, but MDR sufficient, cells are spared. This allows targeted depletion at a higher degree of specificity than has been previously achieved. We have applied this technique to study trogocytosis, the intercellular transfer of cell surface molecules, but this principle could also be adapted using technology already available for use in other fields of study.",

keywords = "Antigen presentation, Cell depletion, Immunotoxin, Molecular transfer, Trogocytosis",

author = "Kathryn Brown and Lucy Meader and Anna Nowocin and Edwards, {Lindsey A.} and Cheung, {Lawrence H.} and Smith, {Richard A.} and Rosenblum, {Michael G.} and Wilson Wong",

year = "2020",

month = aug,

doi = "10.1016/j.jim.2020.112794",

language = "English",

volume = "483",

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Brown, K, Meader, L, Nowocin, A, Edwards, LA, Cheung, LH, Smith, RA, Rosenblum, MG & Wong, W 2020, 'A novel in vivo model using immunotoxin in the absence of p-glycoprotein to achieve ultra selective depletion of target cells: Applications in trogocytosis and beyond', Journal of Immunological Methods, vol. 483, 112794, pp. 1-10. https://doi.org/10.1016/j.jim.2020.112794

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T2 - Applications in trogocytosis and beyond

AU - Brown, Kathryn

AU - Meader, Lucy

AU - Nowocin, Anna

AU - Edwards, Lindsey A.

AU - Cheung, Lawrence H.

AU - Smith, Richard A.

AU - Rosenblum, Michael G.

AU - Wong, Wilson

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AB - A commonly employed method to determine the function of a particular cell population and to assess its contribution to the overall system in vivo is to selectively deplete that population and observe the effects. Using monoclonal antibodies to deliver toxins to target cells can achieve this with a high degree of efficiency. Here, we describe an in vivo model combining the use of immunotoxins and multidrug resistant (MDR) gene deficient mice so that only MDR deficient cells expressing the target molecule would be depleted while target molecule expressing, but MDR sufficient, cells are spared. This allows targeted depletion at a higher degree of specificity than has been previously achieved. We have applied this technique to study trogocytosis, the intercellular transfer of cell surface molecules, but this principle could also be adapted using technology already available for use in other fields of study.

KW - Antigen presentation

KW - Cell depletion

KW - Immunotoxin

KW - Molecular transfer

KW - Trogocytosis

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A novel in vivo model using immunotoxin in the absence of p-glycoprotein to achieve ultra selective depletion of target cells: Applications in trogocytosis and beyond

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