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

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

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
Pages (from-to)	112794
Journal	Journal of Immunological Methods
Volume	483
DOIs	https://doi.org/10.1016/j.jim.2020.112794
Publication status	Published - Aug 2020

Keywords

ATP Binding Cassette Transporter, Subfamily B/deficiency
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism
ATP Binding Cassette Transporter, Subfamily G, Member 2/deficiency
Animals
Cytotoxicity, Immunologic/drug effects
Female
Genes, MDR/physiology
Graft Survival/drug effects
Heart Transplantation
Histocompatibility Antigens Class II/immunology
Immunoconjugates/toxicity
Immunoglobulin Fab Fragments/toxicity
Immunotoxins/toxicity
Kidney Transplantation
Lymphocyte Depletion/methods
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
Ribosome Inactivating Proteins, Type 1/toxicity
Spleen/drug effects
Transplantation Tolerance/drug effects

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10.1016/j.jim.2020.112794

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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, 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 = "ATP Binding Cassette Transporter, Subfamily B/deficiency, ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 2/deficiency, Animals, Cytotoxicity, Immunologic/drug effects, Female, Genes, MDR/physiology, Graft Survival/drug effects, Heart Transplantation, Histocompatibility Antigens Class II/immunology, Immunoconjugates/toxicity, Immunoglobulin Fab Fragments/toxicity, Immunotoxins/toxicity, Kidney Transplantation, Lymphocyte Depletion/methods, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Ribosome Inactivating Proteins, Type 1/toxicity, Spleen/drug effects, Transplantation Tolerance/drug effects",

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",

pages = "112794",

journal = "Journal of Immunological Methods",

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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.

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KW - ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism

KW - ATP Binding Cassette Transporter, Subfamily G, Member 2/deficiency

KW - Animals

KW - Cytotoxicity, Immunologic/drug effects

KW - Female

KW - Genes, MDR/physiology

KW - Graft Survival/drug effects

KW - Heart Transplantation

KW - Histocompatibility Antigens Class II/immunology

KW - Immunoconjugates/toxicity

KW - Immunoglobulin Fab Fragments/toxicity

KW - Immunotoxins/toxicity

KW - Kidney Transplantation

KW - Lymphocyte Depletion/methods

KW - Mice, Inbred C57BL

KW - Mice, Inbred CBA

KW - Mice, Knockout

KW - Ribosome Inactivating Proteins, Type 1/toxicity

KW - Spleen/drug effects

KW - Transplantation Tolerance/drug effects

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DO - 10.1016/j.jim.2020.112794

M3 - Article

C2 - 32428450

SN - 0022-1759

VL - 483

SP - 112794

JO - Journal of Immunological Methods

JF - Journal of Immunological Methods

ER -

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

Keywords

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