Immune Evasion Strategies of Human Poxviruses: A Roadmap for Engineering Low-Immunogenic CAR-Based and iPSC-Derived Cell Products
4 affiliations
- 1Endocrinology Research Centre, 117036 Moscow, Russia
- 2Department of Human Anatomy and Histology, N. V. Sklifosovsky Institute of Clinical Medicine, First Moscow State Medical University (Sechenov University), 125009 Moscow, Russia
- 3Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia
- 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
Abstract
Allogeneic chimeric antigen receptor (CAR)-based cell products and induced pluripotent stem cell (iPSC)-derived regenerative grafts increasingly use multilayer immune engineering. Current strategies are strongest against direct human leukocyte antigen (HLA)-dependent recognition but incompletely address natural killer (NK)-cell counter-pressure, priming by recipient antigen-presenting cells, humoral and complement-mediated injury, inflammatory remodeling, blood- and tissue-interface damage, and terminal cell killing. Poxvirus research has characterized diverse immunomodulatory mechanisms relevant to these barriers. We review poxviral control of interferon signaling, antigen processing and presentation, T-cell activation, NK-cell surveillance, cytokine and chemokine networks, complement, inflammatory signaling, and regulated cell death, integrating viral mechanisms with human perturbation, cell-engineering, and transplantation evidence. A qualitative Tier 1–3 framework distinguishes mechanisms close to current cell-therapy practice from those requiring greater product-specific validation or control. The resulting design rules favor graded antigen-presentation control with paired NK validation, local or transient inflammatory buffering, interface-restricted complement protection, and survival enhancement only when independent eliminability is preserved. Selected poxviral proteins can act autonomously outside productive infection, but direct viral-protein expression remains a selective rather than default option. We propose a conditional defense-in-depth framework in which modules are added only when a residual barrier is demonstrated in the final therapeutic product.
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BibTeX
@article{antonov2026immune,
title = {{Immune Evasion Strategies of Human Poxviruses: A Roadmap for Engineering Low-Immunogenic CAR-Based and iPSC-Derived Cell Products}},
author = {Daniil O. Antonov and Marina Yu. Loguinova and Hui Fan and Elena V. Sazonova and Anastasiia O. Sosnovtseva and Dmitry S. Karpov and Artem D. Molchanov and Vladimir N. Nikolenko and Vladimir P. Chekhonin and Natalia G. Mokrysheva},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201902},
url = {https://www.mdpi.com/2073-4409/15/20/1902},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immune Evasion Strategies of Human Poxviruses: A Roadmap for Engineering Low-Immunogenic CAR-Based and iPSC-Derived Cell Products
AU - Daniil O. Antonov
AU - Marina Yu. Loguinova
AU - Hui Fan
AU - Elena V. Sazonova
AU - Anastasiia O. Sosnovtseva
AU - Dmitry S. Karpov
AU - Artem D. Molchanov
AU - Vladimir N. Nikolenko
AU - Vladimir P. Chekhonin
AU - Natalia G. Mokrysheva
PY - 2026
DA - 2026/10/19
JO - Cells
DO - 10.3390/cells15201902
UR - https://www.mdpi.com/2073-4409/15/20/1902
AB - Allogeneic chimeric antigen receptor (CAR)-based cell products and induced pluripotent stem cell (iPSC)-derived regenerative grafts increasingly use multilayer immune engineering. Current strategies are strongest against direct human leukocyte antigen (HLA)-dependent recognition but incompletely address natural killer (NK)-cell counter-pressure, priming by recipient antigen-presenting cells, humoral and complement-mediated injury, inflammatory remodeling, blood- and tissue-interface damage, and terminal cell killing. Poxvirus research has characterized diverse immunomodulatory mechanisms relevant to these barriers. We review poxviral control of interferon signaling, antigen processing and presentation, T-cell activation, NK-cell surveillance, cytokine and chemokine networks, complement, inflammatory signaling, and regulated cell death, integrating viral mechanisms with human perturbation, cell-engineering, and transplantation evidence. A qualitative Tier 1–3 framework distinguishes mechanisms close to current cell-therapy practice from those requiring greater product-specific validation or control. The resulting design rules favor graded antigen-presentation control with paired NK validation, local or transient inflammatory buffering, interface-restricted complement protection, and survival enhancement only when independent eliminability is preserved. Selected poxviral proteins can act autonomously outside productive infection, but direct viral-protein expression remains a selective rather than default option. We propose a conditional defense-in-depth framework in which modules are added only when a residual barrier is demonstrated in the final therapeutic product.
SN - 2073-4409
ER -