Figure 5.
CISH KO iC9/CAR19/IL-15 NK cells improve tumor control and survival in a Raji lymphoma mouse model at low infusion doses. (A) Schematic diagram representing the timeline of the in vivo experiments. (B) BLI imaging of an independent mouse experiment where mice received either Raji alone or Raji plus 10 × 106 CAR19/IL-15 control or Raji plus 10 × 106 CAR19/IL-15 CISH KO (n = 5 mice per group). *This mouse died accidentally during bleeding. (C) Survival curve for the 3 groups of mice described in panel B (Raji alone, green; Raji plus 10 × 106 CAR19/IL-15 control, blue; Raji plus 10 × 106 CAR19/IL-15 CISH KO, red). Statistical significance is represented by *P ≤ .05 for the comparison of the red and blue curves and **P ≤ .01 for the comparison of the blue and gray curves. (D) Graph representing the body weights of mice over time in the 3 different groups described in panel B. Bars represent mean values with standard deviation. (E) BLI data from 5 groups of NSG mice treated with Raji alone (n = 5), Raji plus 1 dose of 3 × 106 of iC9/CAR19/IL-15 control NK cells (n = 5) or iC9/CAR19/IL-15 CISH KO NK cells (n = 5), or Raji plus 1 dose of 10 × 106 of iC9/CAR19/IL-15 control NK cells (n = 5) or iC9/CAR19/IL-15 CISH KO NK cells (n = 3). (F-G) The average radiance (F) and survival curves (G) are shown for the 5 groups of mice described in panel E. Statistical significance is represented by *P ≤ .05 or **P ≤ .01. (H) Photomicrographs of hematoxylin and eosin (H&E) and immunohistochemical CD20 staining of liver (top) and bone marrow (BM) (bottom) from mice engrafted with Raji B cell lymphoma either untreated or treated with iC9/CAR19/IL-15 CISH KO or iC9/CAR19/IL-15 CTLR NK cells (10 × 106 dose level). Representative images show absence of neoplastic B cells in liver and bone marrow of a mouse treated with iC9/CAR19/IL-15 CISH KO NK cells in comparison with similar treatment with iC9/CAR19/IL-15 NK cells retaining CISH expression. Images were taken at 10× (liver) and 5× (bone marrow) using a Leica DFC 495 camera. (I) Bar graph showing the percentage of NK cells (CD3−CD56+CD45+) present in peripheral blood from mice treated with iC9/CAR19/IL-15 control vs iC9/CAR19/IL-15 CISH KO NK cells at days 7, 14, 21, and 28. Bars represent mean values with standard deviation. Statistical significance is represented by *P ≤ .05 or **P ≤ .01. (J) Graph showing body weights of NSG mice groups described in panel E over time.

CISH KO iC9/CAR19/IL-15 NK cells improve tumor control and survival in a Raji lymphoma mouse model at low infusion doses. (A) Schematic diagram representing the timeline of the in vivo experiments. (B) BLI imaging of an independent mouse experiment where mice received either Raji alone or Raji plus 10 × 106 CAR19/IL-15 control or Raji plus 10 × 106 CAR19/IL-15 CISH KO (n = 5 mice per group). *This mouse died accidentally during bleeding. (C) Survival curve for the 3 groups of mice described in panel B (Raji alone, green; Raji plus 10 × 106 CAR19/IL-15 control, blue; Raji plus 10 × 106 CAR19/IL-15 CISH KO, red). Statistical significance is represented by *P ≤ .05 for the comparison of the red and blue curves and **P ≤ .01 for the comparison of the blue and gray curves. (D) Graph representing the body weights of mice over time in the 3 different groups described in panel B. Bars represent mean values with standard deviation. (E) BLI data from 5 groups of NSG mice treated with Raji alone (n = 5), Raji plus 1 dose of 3 × 106 of iC9/CAR19/IL-15 control NK cells (n = 5) or iC9/CAR19/IL-15 CISH KO NK cells (n = 5), or Raji plus 1 dose of 10 × 106 of iC9/CAR19/IL-15 control NK cells (n = 5) or iC9/CAR19/IL-15 CISH KO NK cells (n = 3). (F-G) The average radiance (F) and survival curves (G) are shown for the 5 groups of mice described in panel E. Statistical significance is represented by *P ≤ .05 or **P ≤ .01. (H) Photomicrographs of hematoxylin and eosin (H&E) and immunohistochemical CD20 staining of liver (top) and bone marrow (BM) (bottom) from mice engrafted with Raji B cell lymphoma either untreated or treated with iC9/CAR19/IL-15 CISH KO or iC9/CAR19/IL-15 CTLR NK cells (10 × 106 dose level). Representative images show absence of neoplastic B cells in liver and bone marrow of a mouse treated with iC9/CAR19/IL-15 CISH KO NK cells in comparison with similar treatment with iC9/CAR19/IL-15 NK cells retaining CISH expression. Images were taken at 10× (liver) and 5× (bone marrow) using a Leica DFC 495 camera. (I) Bar graph showing the percentage of NK cells (CD3−CD56+CD45+) present in peripheral blood from mice treated with iC9/CAR19/IL-15 control vs iC9/CAR19/IL-15 CISH KO NK cells at days 7, 14, 21, and 28. Bars represent mean values with standard deviation. Statistical significance is represented by *P ≤ .05 or **P ≤ .01. (J) Graph showing body weights of NSG mice groups described in panel E over time.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal