Interventional patient dosing and immunity
| . | Patient 1 . | Patient 2 . | Patient 3 . | Patient 4 . | Patient 5∗ . | Patient 6 . | Patient 7 . | Patient 8∗ . | Patient 9∗ . | Patient 10 . | Patient 11 . | Patient 12 . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HLA class I allele matches with CTL donor | A∗02:01 | A∗02:01 | A∗02:01 B∗18:01 | A∗02:01 C∗07:01 | A∗02:01 | A∗02:01 | A∗02:01 | A∗02:01 | A∗02:01 | A∗02:01 | A∗02:01 C∗07:01 | A∗02:01 C∗07:01 |
| Dose level | 1 × 105/kg | 1 × 105/kg | 1 × 105/kg | 3 × 105/kg | 3 × 105/kg | 3 × 105/kg | 1 × 106/kg | 1 × 106/kg | 1 × 106/kg | 3 × 106/kg | 3 × 106/kg | 3 × 106/kg |
| Adjusted weight (kg) | 94.9 | 55.1 | 57.7 | 92.7 | 73.04 | 46.4 | 90.3 | 53.52 | 74.16 | 97.94 | 81 | 104 |
| Total cell dose (10e6) | 9.5 | 5.51 | 5.80 | 27.80 | 21.91 | 13.92 | 90.30 | 53.52 | 74.16 | 294.0 | 243.0 | 312.0 |
| Virus-specific CTL dose (10e6) | 6.51 | 3.77 | 3.97 | 19.04 | 15.01 | 9.54 | 61.86 | 36.66 | 50.80 | 201.39 | 166.46 | 213.72 |
| Anti-HLA donor antibody detected at or after day +28 | None | None | None | None | None | None | None | None | None | None | A∗26, DRB1∗08 | None |
| Vaccine or history of COVID-19 infection before CTLs | No hx Vac No hx Cov | Vac × 2 No hx Cov | Vac × 1 No hx Cov | Vac × 2 No hx Cov | No Vac No hx Cov | Vac × 1 No hx Cov | Vac × 3 No hx Cov | NVR No hx Cov | NVR No hx Cov | Vac × 3 No hx Cov | No Vac Hx of Cov (6 mo prior) | Vac × 3 No hx Cov |
| Antibody status† 1 mo after CTLs | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >1.76 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | No anti-spike antibody | In Allo HSCT | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >184 U/mL |
| +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | No Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | No Anti-NC antibody | In Allo HSCT | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | |
| Antibody status† 2 mo after CTLs | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >1.31 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >1.04 U/mL | In Allo HSCT | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >172.5 U/mL |
| +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | No Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | No Anti-NC antibody | In Allo HSCT | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | |
| Antibody status† 6 mo after CTLs | N/A‡ | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | N/A‡ | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | After Allo HSCT | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >215 U/mL |
| N/A‡ | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | N/A‡ | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | After Allo HSCT | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody |
| . | Patient 1 . | Patient 2 . | Patient 3 . | Patient 4 . | Patient 5∗ . | Patient 6 . | Patient 7 . | Patient 8∗ . | Patient 9∗ . | Patient 10 . | Patient 11 . | Patient 12 . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HLA class I allele matches with CTL donor | A∗02:01 | A∗02:01 | A∗02:01 B∗18:01 | A∗02:01 C∗07:01 | A∗02:01 | A∗02:01 | A∗02:01 | A∗02:01 | A∗02:01 | A∗02:01 | A∗02:01 C∗07:01 | A∗02:01 C∗07:01 |
| Dose level | 1 × 105/kg | 1 × 105/kg | 1 × 105/kg | 3 × 105/kg | 3 × 105/kg | 3 × 105/kg | 1 × 106/kg | 1 × 106/kg | 1 × 106/kg | 3 × 106/kg | 3 × 106/kg | 3 × 106/kg |
| Adjusted weight (kg) | 94.9 | 55.1 | 57.7 | 92.7 | 73.04 | 46.4 | 90.3 | 53.52 | 74.16 | 97.94 | 81 | 104 |
| Total cell dose (10e6) | 9.5 | 5.51 | 5.80 | 27.80 | 21.91 | 13.92 | 90.30 | 53.52 | 74.16 | 294.0 | 243.0 | 312.0 |
| Virus-specific CTL dose (10e6) | 6.51 | 3.77 | 3.97 | 19.04 | 15.01 | 9.54 | 61.86 | 36.66 | 50.80 | 201.39 | 166.46 | 213.72 |
| Anti-HLA donor antibody detected at or after day +28 | None | None | None | None | None | None | None | None | None | None | A∗26, DRB1∗08 | None |
| Vaccine or history of COVID-19 infection before CTLs | No hx Vac No hx Cov | Vac × 2 No hx Cov | Vac × 1 No hx Cov | Vac × 2 No hx Cov | No Vac No hx Cov | Vac × 1 No hx Cov | Vac × 3 No hx Cov | NVR No hx Cov | NVR No hx Cov | Vac × 3 No hx Cov | No Vac Hx of Cov (6 mo prior) | Vac × 3 No hx Cov |
| Antibody status† 1 mo after CTLs | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >1.76 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | No anti-spike antibody | In Allo HSCT | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >184 U/mL |
| +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | No Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | No Anti-NC antibody | In Allo HSCT | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | |
| Antibody status† 2 mo after CTLs | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >1.31 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >1.04 U/mL | In Allo HSCT | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >172.5 U/mL |
| +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | No Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | No Anti-NC antibody | In Allo HSCT | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | |
| Antibody status† 6 mo after CTLs | N/A‡ | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | N/A‡ | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | After Allo HSCT | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >250 U/mL | +Anti-spike antibody >215 U/mL |
| N/A‡ | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | N/A‡ | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody | After Allo HSCT | +Anti-NC antibody | +Anti-NC antibody | +Anti-NC antibody |
Allo HSCT, allogeneic hematopoietic stem cell transplantation; Cov, COVID-19; NC, Nucleocapsid; No hx Cov, no history of COVID-19; No hx Vac, no history of SARS-CoV-2 vaccine; NVR, No vaccine response; Vac, Vaccine.
Patients 5, 8, and 9 under treatment for lymphoma at time of COVID-19. Patient 5 admitted for autologous HSCT 28 days after CTL infusion, underwent HSCT without complication, but died of preexisting, progressive lymphoma 4½ months after CTLs. Patient 9 admitted for successful allogeneic HSCT 16 days after CTL infusion.
Reference range for a positive spike antibody titer is >0.80 U/mL to >250.00 U/mL.
Six-month sample not available due to lost to follow-up after 2½ months, (patient 1) and death at 4½ months, (patient 5).