Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations

Marijn C. Peters; Arnaud Zaldumbide; Esmee J. Groeneveld; Martijn J.W.E. Rabelink; Janneke H. Peerlings; Antoon van den Bogaerdt; Carlijn V.C. Bouten; Rob C. Hoeben; Marie Jose Goumans; Abraham van Wijk

doi:10.1016/j.jacbts.2024.07.003

Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations

Marijn C. Peters
, Arnaud Zaldumbide
, Esmee J. Groeneveld
, Martijn J.W.E. Rabelink
, Janneke H. Peerlings
, Antoon van den Bogaerdt
, Carlijn V.C. Bouten
, Rob C. Hoeben
, Marie Jose Goumans^*
, Abraham van Wijk^*

^*Corresponding author for this work

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

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Abstract

Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen–reactive CD8+ T-cell clone without inducing cytotoxicity. This study demonstrates immune shielding of human heart valves and brings us closer to a durable valve graft in pediatric patients.

Original language	English
Pages (from-to)	1345-1359
Number of pages	15
Journal	JACC. Basic to Translational Science
Volume	9
Issue number	11
Early online date	11 Sept 2024
DOIs	https://doi.org/10.1016/j.jacbts.2024.07.003
Publication status	Published - Nov 2024

Keywords

congenital heart disease
heart valves
immune evasion
tissue bioengineering

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10.1016/j.jacbts.2024.07.003Licence: CC BY-NC-ND

1-s2.0-S2452302X24002602-mainFinal published version, 3.73 MBLicence: CC BY-NC-ND

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Peters, M. C., Zaldumbide, A., Groeneveld, E. J., Rabelink, M. J. W. E., Peerlings, J. H., van den Bogaerdt, A., Bouten, C. V. C., Hoeben, R. C., Goumans, M. J., & van Wijk, A. (2024). Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations. JACC. Basic to Translational Science, 9(11), 1345-1359. https://doi.org/10.1016/j.jacbts.2024.07.003

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title = "Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations",

abstract = "Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen–reactive CD8+ T-cell clone without inducing cytotoxicity. This study demonstrates immune shielding of human heart valves and brings us closer to a durable valve graft in pediatric patients.",

keywords = "congenital heart disease, heart valves, immune evasion, tissue bioengineering",

author = "Peters, \{Marijn C.\} and Arnaud Zaldumbide and Groeneveld, \{Esmee J.\} and Rabelink, \{Martijn J.W.E.\} and Peerlings, \{Janneke H.\} and \{van den Bogaerdt\}, Antoon and Bouten, \{Carlijn V.C.\} and Hoeben, \{Rob C.\} and Goumans, \{Marie Jose\} and \{van Wijk\}, Abraham",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = nov,

doi = "10.1016/j.jacbts.2024.07.003",

language = "English",

volume = "9",

pages = "1345--1359",

journal = "JACC. Basic to Translational Science",

issn = "2452-302X",

publisher = "Elsevier",

number = "11",

}

Peters, MC, Zaldumbide, A, Groeneveld, EJ, Rabelink, MJWE, Peerlings, JH, van den Bogaerdt, A, Bouten, CVC, Hoeben, RC, Goumans, MJ & van Wijk, A 2024, 'Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations', JACC. Basic to Translational Science, vol. 9, no. 11, pp. 1345-1359. https://doi.org/10.1016/j.jacbts.2024.07.003

TY - JOUR

T1 - Immune Shielding of Human Heart Valves

T2 - A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations

AU - Peters, Marijn C.

AU - Zaldumbide, Arnaud

AU - Groeneveld, Esmee J.

AU - Rabelink, Martijn J.W.E.

AU - Peerlings, Janneke H.

AU - van den Bogaerdt, Antoon

AU - Bouten, Carlijn V.C.

AU - Hoeben, Rob C.

AU - Goumans, Marie Jose

AU - van Wijk, Abraham

PY - 2024/11

Y1 - 2024/11

N2 - Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen–reactive CD8+ T-cell clone without inducing cytotoxicity. This study demonstrates immune shielding of human heart valves and brings us closer to a durable valve graft in pediatric patients.

AB - Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen–reactive CD8+ T-cell clone without inducing cytotoxicity. This study demonstrates immune shielding of human heart valves and brings us closer to a durable valve graft in pediatric patients.

KW - congenital heart disease

KW - heart valves

KW - immune evasion

KW - tissue bioengineering

UR - https://www.scopus.com/pages/publications/85204806794

U2 - 10.1016/j.jacbts.2024.07.003

DO - 10.1016/j.jacbts.2024.07.003

M3 - Article

C2 - 39619144

AN - SCOPUS:85204806794

SN - 2452-302X

VL - 9

SP - 1345

EP - 1359

JO - JACC. Basic to Translational Science

JF - JACC. Basic to Translational Science

IS - 11

ER -

Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations

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