Table 8. Microscopic findings following the administration of CART19 in NSG mice.
| Microscopic findings | Organ/tissue | Incidence* | |||
|---|---|---|---|---|---|
| Vehicle control | 0.2×107 cells/mL | 0.6×107 cells/mL | 1.8×107 cells/mL | ||
| Aggregation of CAR-T cells followed by immune-related cells | Liver | ||||
| 14 days after dosing | – | 0/5 | 1/3 | 2/5 | |
| 28 days after dosing | – | 1/2 | 2/3 | 1/5 | |
| Found dead | – | 4/16 | 4/15 | 3/13 | |
| Kidney | |||||
| 14 days after dosing | – | 0/5 | 1/3 | 0/5 | |
| 28 days after dosing | – | 1/2 | 0/3 | 3/5 | |
| Found dead | – | 0/16 | 1/15 | 1/13 | |
| Spleen | |||||
| 14 days after dosing | – | 2/5 | 1/3 | 2/5 | |
| 28 days after dosing | – | 2/2 | 2/3 | 4/5 | |
| Found dead | – | 3/16 | 1/15 | 3/13 | |
| Lung | |||||
| 14 days after dosing | – | 5/5 | 2/3 | 2/5 | |
| 28 days after dosing | – | 2/2 | 2/3 | 4/5 | |
| 56 days after dosing | – | 1/1 | – | – | |
| Found dead | – | 7/16 | 9/15 | 9/13 | |
| Heart | |||||
| 14 days after dosing | – | 0/5 | 0/3 | 1/5 | |
| Found dead | – | 0/16 | 0/15 | 2/13 | |
| Brain | |||||
| 28 days after dosing | – | 0/2 | 1/3 | 0/5 | |
| 56 days after dosing | – | 1/1 | – | – | |
| Found dead | – | 0/16 | 2/15 | 1/13 | |
| Duodenum (found dead) | – | 2/16 | 0/15 | 0/13 | |
| Jejunum | |||||
| 14 days after dosing | – | 1/5 | 0/3 | 1/5 | |
| 28 days after dosing | – | 2/2 | 1/3 | 2/5 | |
| Found dead | – | 1/16 | 0/15 | 1/13 | |
| Ileum, capsule | |||||
| 14 days after dosing | – | 0/5 | 0/3 | 1/5 | |
| 28 days after dosing | – | 0/2 | 0/3 | 1/5 | |
| Colon (found dead) | – | 0/16 | 1/15 | 0/13 | |
| Epididymis (found dead) | – | 1/8 | 0/6 | 1/6 | |
| Fibrosis | Liver | ||||
| 28 days after dosing | – | 1/2 | 0/3 | 1/5 | |
| Found dead | – | 0/16 | 0/15 | 1/13 | |
| Aggregation of foam-like macrophages | Spleen | – | 1/2 | 0/3 | 1/5 |
| 28 days after dosing | – | 1/2 | 0/3 | 1/5 | |
| 56 days after dosing | – | 1/1 | – | – | |
| Found dead | – | 1/16 | 4/15 | 5/13 | |
| Suppurative inflammation | Heart (found dead) | 1/22 | 0/16 | 0/15 | 0/13 |
| Brain (found dead) | 0/22 | 1/16 | 1/15 | 0/13 | |
| Hepatocyte necrosis | Liver (found dead) | 0/22 | 1/16 | 0/15 | 0/13 |
| Infarction | Kidney | ||||
| Found dead | 2/22 | 5/16 | 7/15 | 6/13 | |
| 56 days after dosing | – | 1/1 | – | – | |
| Suppurative inflammation with tubular necrosis | Kidney, papilla (found dead) | 2/22 | 2/16 | 2/15 | 5/13 |
| Decreased bone marrow cells | Bone marrow (found dead) | 9/22 | 3/16 | 0/15 | 1/13 |
*, total number of males and females found these microscopic changes/total number of males and females examined by microscopy in each group. When the tissue autolysis was found in dead animal, the histopathological examination wasn’t performed. The microscopic findings in all tissues/organs was recorded by histopathological examination on the day 14, day 28, and day 56 after administration, respectively. In addition, the microscopic findings of dead/moribund animals were listed separately for each group during the 56-day trial period. –: there was no this histopathological change in the tissue/organ. CAT-T, chimeric antigen receptor-modified T.