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. 2023 May 16;31(7):2132–2153. doi: 10.1016/j.ymthe.2023.05.009

Figure 4.

Figure 4

CER-1236 has potent anti-tumor effects against a xenograft model of REC-1 MCL

(A) Schematic of xenograft study. 5e-6 REC-1 stably expressing fLuc were injected intravenously into NSG mice at day 2. On day 1, mice were administered 8 mg/kg/day of ibrutinib via their drinking water. Mice were administered 7.5e-6 CER-1236+ T cells i.v. on day 0. Tumor burden was assessed twice per week by BLI measurement, and blood was drawn weekly to assess CER-1236 T cell expansion. At day 16, organs were collected from ibrutinib-treated mice for IHC and H&E staining. (B) CER-1236 treatment eliminates REC-1 tumors. BLI images of mice taken at the indicated days post T cell transfusion. X indicates animals removed due to reaching BLI maximum, ∗ indicates animals removed for timed takedown. (C) Average BLI ± SEM shown for each group. N for each group indicated in legend. Data are representative of two experiments using different donors. (D) CER-1236 treatment improves survival in NSG mice with REC-1 MCL xenografts. Probability of survival shown for mice treated with CER-1236 or control groups. Mice were removed from study upon reaching BLI maximum of 1e-8 photons/s or upon displaying signs of GvHD. Data are representative of two experiments using different donors. (E) CER-1236 expansion peaks at 7 days post administration and decreases after. DNA was isolated from peripheral blood and frequency of CER-1236 T cells was determined by ddPCR using a CER-specific primer/probe set. Cells/μL of blood was determined by: probe counts × (volume of ddPCR reaction/μL DNA used). Longitudinal analysis is shown for each mouse in the indicated groups. (F) Anti-human CD3 IHC staining of select organs. At day 16 post T cell transfusion, untransduced CER-1236-treated animals receiving ibrutinib were sacrificed and organs were removed for IHC. Representative images of 20× images of liver, lung, kidney, myocardium, and brain are shown. Brown areas indicate CD3 detection. Scale bars, 200 μm. i.v., intravenous; CER, chimeric engulfment receptor; UNT, untransduced; SEM, standard error of the mean; BLI, bioluminescence imaging.