Page 289 - Haematologica March 2020

Long-term eradication of ENKL by rejuvenated CTL
combined use of anti-PD-1 Ab with either original CTL (P=0.13) or rejT (P=0.37). Collectively, although both origi- nal CTL and rejT exhibited strong anti-tumor effects against ENKL during the three-week observation period, only LMP2-rejT, whether or not anti-PD-1 Ab was given, dis- tinctly improved long-term survival in ENKL-bearing mice.
LMP2-rejT treatment completely eliminated ENKL and rejT persisted in long-term survivor mice
We euthanized mice engrafted with ENKL tumors and that had survived 211 days after the fisrt injection of LMP2-rejT ± anti-PD-1 Ab. The heart, lungs, esophagus, stomach, pancreas, liver, colon, kidneys, spleen, and bone
AB
C
Days after T-cell transfer
Figure 4. Induced pluripotent stem cell-derived-derived LMP2-rejT display superior anti-extranodal NK/T-cell lymphoma, nasal type activity in vivo. (A) Bioluminescence imaging of mice treated either with original LMP2-CTL or LMP2-rejT. FFluc+ENKL-bearing mice were divided into six groups that received no treat- ment (n=6), anti-PD-1 Ab (n=6), original CTL (n=6), original CTL + anti-PD-1 Ab (n=6), RejT (n=6), or RejT + anti-PD-1 Ab (n=5). Images of three representative mice from each group are shown. (B) Quantification of total tumor growth on day 21 after treatment is represented as log10 signal change. Error bars represent ± SD. ****P<0.0001, ***P<0.001 and *P<0.05 by one-way ANOVA. (C) Kaplan-Meier survival curves representing percentage survival for treated and control mice: tumor only or treated with anti-PD-1 Ab, original CTL, original CTL + anti-PD-1 Ab, RejT, or RejT + anti-PD-1 Ab. **P<0.01 and *P<0.05 by the log-rank test. iPSC: induced pluripotent stem cell; LMP: latent membrane protein; rejT: rejuvenated cytotoxic T lymphocytes; ENKL: extranodal NK/T-cell lymphoma, nasal type; FFluc: firefly luciferase; CTL: cytotoxic T lymphocytes; PD-1: programmed cell death 1; Ab: antibody; SD: standard deviation.
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