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. 2020 May 17;23(6):101162. doi: 10.1016/j.isci.2020.101162

Figure 2.

Figure 2

Overview of Genetic Modification Strategies Employed to Generate Hypoimmunogenic Cells

Allogeneic cells can be rejected through innate immunity (NK cells and macrophages) as well as adaptive immunity (T cells).

(A) Allogeneic cells activate T cells by HLA-I and HLA-II molecules. HLA-I molecules suppress NK cells.

(B) Elimination of HLA-I by knocking out B2M and elimination of HLA-II by knocking out CIITA can evade T cell surveillance but trigger NK cell activity.

(C) Elimination of HLA-I and HLA-II to evade T cell attack combined with expression of the CD47 molecules to inactivate NK cells and macrophages (Deuse et al., 2019).

(D) Simultaneous deletion of HLA-A/B and HLA-II genes, and not HLA-C, allows HLA-C/G and HLA-E to suppress NK cells (Xu et al., 2019).

(E) Simultaneous knockout of HLA-A/B/C and HLA-II combined with expression of the immunomodulatory factors PD-L1, HLA-G, and CD47 (Han et al., 2019). These strategies combined can make the engineered cells to evade immune surveillance by T cells, NK cells, and macrophages.

Orange lines and blue lines depict pathway activation and suppression, respectively. NK, natural killer; Th, T helper; MAC, macrophage; CTL, cytotoxic lymphocyte.