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. 2022 Feb 14;23(4):e52904. doi: 10.15252/embr.202152904

Figure 5. 4D7 blocks mutant CALR‐dependent proliferation in vivo and prolongs survival.

Figure 5

  1. Illustration showing bone marrow NSG engraftment model with TPO‐independent TF‐1 TpoR CALRdel61 cells treated with 4D7 or IgG control twice weekly, starting 7 days after engraftment via intraperitoneal injection and final measurements taken from euthanized mice.
  2. Pharmacokinetic measurements of serum levels of 4D7 in mice after intraperitoneal injection at 0, 1, 24, 48, 72 and 110 h since administration.
  3. Percentage of TF‐1 TpoR CALRdel61 human CD33+ cells measured in peripheral blood at 3 weeks post‐tail vein engraftment (n = 5 mice per treatment).
  4. Kaplan–Meier survival curve of bone marrow engraftment model of TF‐1 TpoR CALRdel61 cells showing improved survival of mice treated with 4D7 compared with IgG control commencing 1 week after tail vein injection (n = 5 mice per treatment).
  5. Mean tumour volume at 21 days after subcutaneous injection of TF‐1 TpoR CALRdel61 cells following treatment with 4D7 or IgG. Cells were pre‐treated with 4D7 or IgG control for 1 h prior to injection and treatment continued twice weekly at 12.5 mg/kg until euthanasia (n = 3 mice per treatment).
  6. Kaplan–Meier survival curve of TF‐1 TpoR CALRdel61 chloroma mice treated with 4D7 or IgG until humane killing due to tumour diameter > 30 mm or ulceration (n = 3 mice per treatment).
  7. Kaplan–Meier survival curve of NSG mice engrafted with ruxolitinib‐resistant TF‐1 TpoR CALRdel61 treated with 12.5 mg/kg 4D7 or IgG twice weekly (n = 5 and 6 mice for IgG and 4D7, respectively).

Data information: For (C and E), a Student's unpaired t‐test was used to determine statistical significance. For all survival curves, the log‐rank Mantel–Cox test P‐value is shown.