Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

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Standard

Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells. / Spiess, Katja; Jeppesen, Mads G.; Malmgaard-Clausen, Mikkel; Krzywkowski, Karen; Kledal, Thomas N.; Rosenkilde, Mette M.

I: Journal of Immunology Research, Bind 2017, 4069260, 2017.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Spiess, K, Jeppesen, MG, Malmgaard-Clausen, M, Krzywkowski, K, Kledal, TN & Rosenkilde, MM 2017, 'Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells', Journal of Immunology Research, bind 2017, 4069260. https://doi.org/10.1155/2017/4069260

APA

Spiess, K., Jeppesen, M. G., Malmgaard-Clausen, M., Krzywkowski, K., Kledal, T. N., & Rosenkilde, M. M. (2017). Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells. Journal of Immunology Research, 2017, [4069260]. https://doi.org/10.1155/2017/4069260

Vancouver

Spiess K, Jeppesen MG, Malmgaard-Clausen M, Krzywkowski K, Kledal TN, Rosenkilde MM. Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells. Journal of Immunology Research. 2017;2017. 4069260. https://doi.org/10.1155/2017/4069260

Author

Spiess, Katja ; Jeppesen, Mads G. ; Malmgaard-Clausen, Mikkel ; Krzywkowski, Karen ; Kledal, Thomas N. ; Rosenkilde, Mette M. / Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells. I: Journal of Immunology Research. 2017 ; Bind 2017.

Bibtex

@article{20438bd6689d4b91be0c7fc26eb12fc9,
title = "Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells",
abstract = "Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin A (PE). Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1) altered chemokine sequence (K14A, F49L, and F49E), (2) shortened and elongated linker region, and (3) modified toxin domain. Only F49L-FTP displayed higher selectivity in its binding to US28 versus CX3CR1, the endogenous receptor for CX3CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate for HCMV treatment. Many viruses encode internalizing receptors suggesting that not only HCMV but also, for instance, Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus may be targeted by FTPs.",
author = "Katja Spiess and Jeppesen, {Mads G.} and Mikkel Malmgaard-Clausen and Karen Krzywkowski and Kledal, {Thomas N.} and Rosenkilde, {Mette M.}",
year = "2017",
doi = "10.1155/2017/4069260",
language = "English",
volume = "2017",
journal = "Journal of Immunology Research",
issn = "2314-8861",
publisher = "Hindawi Publishing Corporation",

}

RIS

TY - JOUR

T1 - Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

AU - Spiess, Katja

AU - Jeppesen, Mads G.

AU - Malmgaard-Clausen, Mikkel

AU - Krzywkowski, Karen

AU - Kledal, Thomas N.

AU - Rosenkilde, Mette M.

PY - 2017

Y1 - 2017

N2 - Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin A (PE). Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1) altered chemokine sequence (K14A, F49L, and F49E), (2) shortened and elongated linker region, and (3) modified toxin domain. Only F49L-FTP displayed higher selectivity in its binding to US28 versus CX3CR1, the endogenous receptor for CX3CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate for HCMV treatment. Many viruses encode internalizing receptors suggesting that not only HCMV but also, for instance, Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus may be targeted by FTPs.

AB - Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin A (PE). Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1) altered chemokine sequence (K14A, F49L, and F49E), (2) shortened and elongated linker region, and (3) modified toxin domain. Only F49L-FTP displayed higher selectivity in its binding to US28 versus CX3CR1, the endogenous receptor for CX3CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate for HCMV treatment. Many viruses encode internalizing receptors suggesting that not only HCMV but also, for instance, Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus may be targeted by FTPs.

U2 - 10.1155/2017/4069260

DO - 10.1155/2017/4069260

M3 - Journal article

C2 - 28251165

VL - 2017

JO - Journal of Immunology Research

JF - Journal of Immunology Research

SN - 2314-8861

M1 - 4069260

ER -

ID: 174665458