Figure 6.
MPC inhibition during CAR T cell in vitro activation and expansion induces superior antitumor activity upon ACT in a mouse melanoma model
(A) Tumor growth following ACT of DMSO or UK5099 (MPCi)-conditioned OT1 T cells.
(B and C) Number of transferred cells (B) and their percentage of TCM (C) in the spleen.
(D–H) Number of tumor-infiltrating transferred cells per milligram of tumor (D) and their percentage of TCF1-positive cells (E), Tpex (F), Tex (G), and cells co-expressing PD1, LAG3, and TIM3 (H).
(I) Number of tumor-infiltrating transferred cells co-expressing IFNγ and TNF.
In (A)–(I), n = 11 mice (DMSO) and 14 mice (MPCi); pooled data from 2 independent experiments.
(J and K) Tumor growth (J) and weight (K) of B16-HER2 tumors following treatment with DMSO or MPCi-conditioned HER2-CAR or BFP control T cells.
(L and M) Percentage of TCM cells (L) and TCF1-expressing cells (M) out of HER2-CAR-positive cells in the blood 12 days after ACT.
(N and O) Number of HER2-CAR-positive cells (N) and their percentage of TCM (O) in the tumor-draining lymph node.
(P and Q) Number of HER2-CAR-positive cells (P) and their percentage of TCF1-positive cells (Q) in the spleen.
(R–V) Number of tumor-infiltrating HER2-CAR-positive cells per milligram of tumor (R) and their percentage of TCF1-positive cells (S), Tpex (T), Tex (U), and cells co-expressing PD1 and TIM3 (V).
In (J)–(V), n = 11 mice (untreated), 4–5 mice (DMSO- and MPCi-BFP-T ACT), 12–13 mice (DMSO- and MPCi-HER2-CAR T ACT). BFP data are derived from 1 experiment; untreated and HER2-CAR T cell transfer is pooled data from 2 independent experiments.
Data are represented as mean ± SEM. Statistics are based on unpaired, two-tailed Student’s t test (A–I and L–V) or one-way ANOVA (J and K), ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001, and ns (p > 0.05). See also Figure S6.