Fig. 6

PVR and PVRL2 double-knockout cells recapitulate antibody effects in vitro and prolong the survival of NSG mice reconstituted with human T cells in vivo. By using CRISPR/Cas9, a polyclonal population of MV4-11 harboring double-knockout cells of PVR and PVRL2 was generated. Either MV4-11 wildtype or double-knockout cells were incubated with HD-PBMCs (a) or CD3⁺ cells (b) for 24 h without or with AMG 330. For statistical analysis, Mann–Whitney U-tests were performed (#p ≤ 0.05; *p ≤ 0.001, n = 3). c Immunodeficient NSG mice were transplanted with either MV4-11 wildtype (WT) cells or PVR- and PVRL2-double-knockout (KO) cells and reconstituted with human T cells. Treatment consisted of daily intraperitoneal application of either placebo (n = 13 for WT and n = 12 for KO) or 15 µg/kg AMG 330 (n = 12 for WT and n = 15 for KO). Log-rank tests were performed: WT placebo vs. KO placebo p < 0.001; WT AMG 330 vs. KO AMG 330 p < 0.001; WT placebo vs. WT AMG 330 p = 0.003; KO placebo vs. KO AMG 330 p = 0.027