Clinical-scale photodepletion experiments (N = 9)
| Exp no. . | Stim . | HLA-type/Stim . | Resp . | HLA-type/Resp . | HLA disparity . | Stimulator T-cell selection . | PD: TH9402, μM . | Readout assay . | Readout time point(s), days after PD . |
|---|---|---|---|---|---|---|---|---|---|
| I | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,26 B-38,58 DR-04,12 | Mismatched (0/6) | None | 5.0/7.5 | MLR | +1/+4 |
| II | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,29 B-44,44 DR-07,11 | Mismatched (0/6) | None | 5.0/7.5 | MLR | +1/+4 |
| III | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,26 B-38,58 DR-04,12 | Mismatched (0/6) | None | 5.0/7.5 | MLR | +1/+4 |
| IV | PAT | A-02,23 B-44,51 DR-04,07 | MSD | A-02,23 B-44,51 DR-04,07 | Matched (6/6) | CD3+ microbeads | 7.5 | HTLp | +1 |
| V | PAT | A-02,68 B-35,39 DR-04,16 | MSD | A-02,68 B-35,39 DR-04,16 | Matched (6/6) | CD3+ microbeads | 7.5 | HTLp | +1 |
| VI | PAT | A-01,03 B-07,57 DR-15,15 | MSD | A-01,03 B-07,57 DR-15,15 | Matched (6/6) | CD3+ microbeads | 7.5 | HTLp | +4 |
| VII | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-01,25 B-18,35 DR-11,12 | Mismatched (2/6) | CD3+ microbeads | 5.0/7.5 | MLR | +0/+1 |
| VIII | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,29 B-44,44 DR-07,11 | Mismatched (0/6) | CD3+ microbeads | 5.0/7.5 | MLR | +0/+1 |
| IX | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,26 B-38,58 DR-04,12 | Mismatched (0/6) | CD3+ microbeads | 5.0/7.5 | MLR | +0/+1 |
| Exp no. . | Stim . | HLA-type/Stim . | Resp . | HLA-type/Resp . | HLA disparity . | Stimulator T-cell selection . | PD: TH9402, μM . | Readout assay . | Readout time point(s), days after PD . |
|---|---|---|---|---|---|---|---|---|---|
| I | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,26 B-38,58 DR-04,12 | Mismatched (0/6) | None | 5.0/7.5 | MLR | +1/+4 |
| II | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,29 B-44,44 DR-07,11 | Mismatched (0/6) | None | 5.0/7.5 | MLR | +1/+4 |
| III | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,26 B-38,58 DR-04,12 | Mismatched (0/6) | None | 5.0/7.5 | MLR | +1/+4 |
| IV | PAT | A-02,23 B-44,51 DR-04,07 | MSD | A-02,23 B-44,51 DR-04,07 | Matched (6/6) | CD3+ microbeads | 7.5 | HTLp | +1 |
| V | PAT | A-02,68 B-35,39 DR-04,16 | MSD | A-02,68 B-35,39 DR-04,16 | Matched (6/6) | CD3+ microbeads | 7.5 | HTLp | +1 |
| VI | PAT | A-01,03 B-07,57 DR-15,15 | MSD | A-01,03 B-07,57 DR-15,15 | Matched (6/6) | CD3+ microbeads | 7.5 | HTLp | +4 |
| VII | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-01,25 B-18,35 DR-11,12 | Mismatched (2/6) | CD3+ microbeads | 5.0/7.5 | MLR | +0/+1 |
| VIII | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,29 B-44,44 DR-07,11 | Mismatched (0/6) | CD3+ microbeads | 5.0/7.5 | MLR | +0/+1 |
| IX | VUD | A-01,24 B-14,35 DR-14,15 | VUD | A-02,26 B-38,58 DR-04,12 | Mismatched (0/6) | CD3+ microbeads | 5.0/7.5 | MLR | +0/+1 |
Six HLA-mismatched (Exp I-III, VII-IX) and 3 HLA-matched (Exp IV-VI) experiments were performed. Irradiated, expanded lymphocytes were used as allostimulators and either grown from PBMCs (Exp I-III) or from CD3+-selected cells (Exp IV-IX). In mismatch experiments, 2 different doses of TH9402 were used. Readouts were performed by MLR in mismatched pairs and by HTLP in matched pairs at different time points after photodepletion.
Stim indicates stimulator; Resp, responder; VUD, volunteer unrelated donor; PAT, patient; and MSD, matched sibling donor.