2024-01-16 アリゾナ大学
◆今後は特定の病気のモデルでの実験や臨床試験が進む見通しで、研究者はこの技術が臨床的に有望であるとしています。同時に、この技術を商業化するClade Therapeutics社が、がんや自己免疫疾患の治療において幹細胞由来の免疫細胞を利用するプラットフォームを確立し、年内に臨床試験を開始する予定です。
<関連情報>
- https://news.arizona.edu/story/study-shows-genetically-modified-pluripotent-stem-cells-may-evade-immunological-rejection
- https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(23)00496-4
異種移植の障壁を回避するためのヒト多能性幹細胞株操作 Engineering human pluripotent stem cell lines to evade xenogeneic transplantation barriers
Hannah A. Pizzato,Paula Alonso-Guallart,James Woods,Jon P. Connelly,Todd A. Fehniger,John P. Atkinson,Shondra M. Pruett-Miller,Frederick J. Monsma Jr.,Deepta Bhattacharya
Stem Cell Reports Published:January 11, 2024
DOI:https://doi.org/10.1016/j.stemcr.2023.12.003
Highlights
•hPSCs were engineered for xenogeneic transplantation in immunocompetent mice
•hPSCs were devoid of HLA-I and -II as well as MICA and MICAB
•Inhibition of both NK cells and complement allowed graft persistence
•Inhibition of phagocytosis was not required for graft persistence
Summary
Successful allogeneic human pluripotent stem cell (hPSC)-derived therapies must overcome immunological rejection by the recipient. To build reagents to define these barriers, we genetically ablated β2M, TAP1, CIITA, CD74, MICA, and MICB to limit expression of HLA-I, HLA-II, and natural killer (NK) cell activating ligands in hPSCs. Transplantation of these cells that also expressed covalent single chain trimers of Qa1 and H2-Kb to inhibit NK cells and CD55, Crry, and CD59 to inhibit complement deposition led to persistent teratomas in wild-type mice. Transplantation of HLA-deficient hPSCs into mice genetically deficient in complement and depleted of NK cells also led to persistent teratomas. Thus, T cell, NK cell, and complement evasion are necessary to prevent immunological rejection of hPSCs and their progeny. These cells and versions expressing human orthologs of immune evasion factors can be used to define cell type-specific immune barriers and conduct preclinical testing in immunocompetent mouse models.
