Treatment schedule, circulating CAR T cells, and development of anti-CAR immunity
| Cohort/patient . | Infusion, d* . | CAR T cells infused, ×109 . | No. of IL-2 doses . | Observation period, d . | Circulating CAR T cells† detection period, d . | Circulating CAR DNA detection period, d . | Human anti–CAIX-CAR antibodies . | Anti-CAR cellular immunity detection first/last day . | |
|---|---|---|---|---|---|---|---|---|---|
| Detection first/last day . | Peak day/ level, ng/mL . | ||||||||
| 1 | |||||||||
| 1 | 1-4‡ | 2.1 | 9 | 1-57 | 3-23 | tfd | 37/57 | 57‖/706 | ne |
| 2 | 1-5, 17-19 | 0.85 | 36 | 1-100 | 3-17:18-32 | tfd-17:18-53 | 100/100 | 100‖/190 | 60/60‖ |
| 3 | 1-4‡ | 0.38 | 9 | 1-240 | 3-12 | 3-32 | 79/240 | 79/292 | 38/240 |
| 2 | |||||||||
| 4 | 1-5, 29-33 | 1.0 | 40 | 1-184 | 3-29:30-39 | 3-29:30-50 | 50/184 | 95/686 | 36/184 |
| 5 | 1-5, 29-33 | 1.0 | 40 | 1-180 | 2-29:30-35 | 2-29:30-35 | —/—¶ | —/— | 36/180 |
| 6 | 1-5, 29-33§ | 1.0 | 35 | 1-276 | 2-29:30-44 | 2-29:30-51 | 44/276 | 86/1241 | 36/122‖ |
| 7 | 1-5, 29-33 | 1.0 | 40 | 1-180 | 2-29:30-51 | 2-29:30-51 | 86/86 | 86/20 | 86/180 |
| 8 | 1-3‡ | 0.3 | 7 | 1-23 | 2-15 | 2-15 | —/—¶ | —/— | ne |
| 3 | |||||||||
| 9 | 1-5, 29-33 | 1.0 | 40 | 1-256 | 2-29:30-51 | 2-29:30-51 | —/—¶ | —/— | 36/50# |
| 10 | 1-5, 29-33 | 1.0 | 40 | 1-198 | 2-29:30-53 | 2-29:30-53 | —/—¶ | —/— | 51/86‖ |
| 11 | 1-5, 36-40 | 1.0 | 40 | 1-74 | 2-36:37-74 | 2-36:37-74 | —/—¶ | —/— | 58#/74# |
| Cohort/patient . | Infusion, d* . | CAR T cells infused, ×109 . | No. of IL-2 doses . | Observation period, d . | Circulating CAR T cells† detection period, d . | Circulating CAR DNA detection period, d . | Human anti–CAIX-CAR antibodies . | Anti-CAR cellular immunity detection first/last day . | |
|---|---|---|---|---|---|---|---|---|---|
| Detection first/last day . | Peak day/ level, ng/mL . | ||||||||
| 1 | |||||||||
| 1 | 1-4‡ | 2.1 | 9 | 1-57 | 3-23 | tfd | 37/57 | 57‖/706 | ne |
| 2 | 1-5, 17-19 | 0.85 | 36 | 1-100 | 3-17:18-32 | tfd-17:18-53 | 100/100 | 100‖/190 | 60/60‖ |
| 3 | 1-4‡ | 0.38 | 9 | 1-240 | 3-12 | 3-32 | 79/240 | 79/292 | 38/240 |
| 2 | |||||||||
| 4 | 1-5, 29-33 | 1.0 | 40 | 1-184 | 3-29:30-39 | 3-29:30-50 | 50/184 | 95/686 | 36/184 |
| 5 | 1-5, 29-33 | 1.0 | 40 | 1-180 | 2-29:30-35 | 2-29:30-35 | —/—¶ | —/— | 36/180 |
| 6 | 1-5, 29-33§ | 1.0 | 35 | 1-276 | 2-29:30-44 | 2-29:30-51 | 44/276 | 86/1241 | 36/122‖ |
| 7 | 1-5, 29-33 | 1.0 | 40 | 1-180 | 2-29:30-51 | 2-29:30-51 | 86/86 | 86/20 | 86/180 |
| 8 | 1-3‡ | 0.3 | 7 | 1-23 | 2-15 | 2-15 | —/—¶ | —/— | ne |
| 3 | |||||||||
| 9 | 1-5, 29-33 | 1.0 | 40 | 1-256 | 2-29:30-51 | 2-29:30-51 | —/—¶ | —/— | 36/50# |
| 10 | 1-5, 29-33 | 1.0 | 40 | 1-198 | 2-29:30-53 | 2-29:30-53 | —/—¶ | —/— | 51/86‖ |
| 11 | 1-5, 36-40 | 1.0 | 40 | 1-74 | 2-36:37-74 | 2-36:37-74 | —/—¶ | —/— | 58#/74# |
tfd indicates too few data points to allow data assessment; and ne, not evaluable. Patient 1: treatment with corticosteroids at days 8-36; patient 8: last blood collection at day 23.
Treatment schedule: CAR T-cell infusion days: cohort 1, days 1-5 and days 17-19, cohort 2 and 3, days 1-5 and days 29-33 (patient 11 days 36-40); IL-2 doses: 5 × 105 IU/m2/12 hours at days 1-10 (patient 1-11) and days 17-26 (patient 1-3) or days 29-38 (patient 4-10; patient 11 days 36-45); Second treatment cycle patient 11 was postponed for 7 days due to a line infection.
Detection (days) during and after treatment cycle 1: treatment cycle 2; assay sensitivity (lower limit of detection) anti-CAR Id flow cytometry: 0.06% of CD3 T cells (patients 1-3) and 0.01% of CD3 T cells (patients 4-11).
Treatment stopped due to SEA ≥ grade 3 liver toxicities.
Patient developed grade 3 liver toxicities after completion of CAR T-cell infusions.
No anti-CAIX-CAR antibody detected during observation period.
Last day of observation.
Very weak or poorly reproducible responses.