Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations
Publication date
2024-11
Authors
Peters, Marijn C
Zaldumbide, Arnaud
Groeneveld, Esmee J.
Rabelink, Martijn J.W.E.
Peerlings, Janneke H.
van den Bogaerdt, Antoon
Bouten, Carlijn V.C.
Hoeben, Rob C.
Goumans, Marie Jose
van Wijk, A
Editors
Advisors
Supervisors
Document Type
Article
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cc_by_nc_nd
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, Cardiology and Cardiovascular Medicine
Citation
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, vol. 9, no. 11, pp. 1345-1359. https://doi.org/10.1016/j.jacbts.2024.07.003