Figure 5. CD3CAR NK-92 cells demonstrate profound anti-leukemic effects in vivo.
A. Elimination of luciferase-expressing Jurkat cells in xenografted mice treated with CD3CAR NK-92 as measured via IVIS imaging. NSG mice were sublethally irradiated and, after 24 hours, intravenously injected with 1 × 106 luciferase-expressing Jurkat cells (Day 0) to induce measurable tumor formation. Three days (Day 3) following Jurkat cell injection, mice were intravenously injected via tail vein with one course consisting of a total of 15 × 106 CD3CAR NK-92 cells or vector control NK-92 cells (N = 6 per group) during the window of the NK cell life expectancy ending on Day 10. On Day 10, two mice died most likely as a result of stroke from injection procedure and NK cell aggregation. Two additional low dose injections totaling 5 × 106 CD3CAR NK-92 cells were administered through Day 14 and 23 to see if this tumor control could be maintained. On days 4, 7, 9, and 13, mice were injected subcutaneously with RediJect D-Luciferin and subjected to IVIS imaging. The % cell lysis by CD3CAR NK-92 relative to control was determined via luciferin signal. B. CD3CAR NK-92 controls Jurkat tumor growth in vivo. Average light intensity (in photons per second) measured for the CD3CAR NK-92 injected mice was compared to that of vector control NK-92 injected mice. P-values are indicated at specific time-points, demonstrating a statistically significant reduction in the relative tumor burden by CD3CAR NK-92 cells as compared to vector control. A zoomed in version of the graph from Days 4-9 is included to better illustrate the error measurements and tumor growth. C. CD3CAR NK-92 reduces Jurkat tumor burden in vivo. Percent luciferin signal measured for CD3CAR NK-92 injected mice and demonstrated as percent difference in signal from vector control NK-92 injected mice. The percent reduction in the tumor burden calculated on days 4, 7, 9, 13, and 17. D. CD3CAR NK-92 treated mice survive significantly longer than control. Kaplan-Meier survival curve for CD3CAR NK-92 treated mice compared to vector control treated mice. Log-rank (Mantel-Cox) test p-values as shown and on Day 43, all CD3CAR-treated mice sacrificed for persistency studies. Two mice that died from the injection procedure were excluded from the survival curve and statistics calculation.