Page 287 - Haematologica March 2020

Long-term eradication of ENKL by rejuvenated CTL
body, P=0.0002; one-way ANOVA). Treatment enhance- ment was not clearly observed with concomitant anti-PD1 antibody therapy either in the original CTL group (P>0.99, one-way ANOVA) or in the rejT group (P>0.99, one-way ANOVA). These three-week observations in vivo demon- strated the tumor suppressive effects against ENKL cells of the original CTL treatment, with more pronounced anti- tumor effects of the rejT treatment.
On long-term observation, original CTL did not prolong survival versus no-treatment controls (P=0.09). Treatment
A
with rejT markedly prolonged survival (mean 239 days, 58-296 days) compared to treatment with original CTL (P=0.03, mean 74.5 days, 58-140 days), with original CTL with anti-PD-1Ab (P=0.01, mean 45.5 days, 34-98 days), and with no treatment (P=0.01) (Figure 4C). RejT with anti-PD-1 Ab also significantly improved survival (mean 134 days, 72-204 days) compared to treatment with origi- nal CTL with anti-PD-1 Ab (P=0.008) and with no treat- ment (P=0.004, mean 58 days, 42-84 days).
No significant survival advantage was observed for the
B
C
Figure 2. Extranodal NK/T-cell lymphoma, nasal type cell lines are sensitive to killing by induced pluripotent stem cell-derived LMP1- and LMP2-rejT in vitro. (A) Flow cytometric EBV LMP2 tetramer analysis of original peripheral blood-derived EBV-CTL and iPSC-derived-EBV-rejT generated from healthy donors. (B) Flow cyto- metric EBV LMP1 and LMP2 tetramer analysis of original peripheral blood-derived EBV-CTL and iPSC-derived-EBV-rejT generated from an ENKL patient (Pt 6). (C) In vitro 51Cr release assay of LMP1- and LMP2-rejT (effectors) against ENKL (targets) and HLA mismatched LCL (control targets). ENKL: extranodal NK/T-cell lymphoma, nasal type; iPSC: induced pluripotent stem cell; LMP: latent membrane protein; rejT: rejuvenated cytotoxic T lymphocytes; EBV: Epstein-Barr virus; Pt: patient; CTL: cytotoxic T lymphocytes; HLA: human leukocyte antigen; LCL: EBV-infected lymphoblastoid cells.
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