Introduction
Patients and methods
Workflow and clinical design
Patients No | B001 | B002 | B003 | B004 | B005 | B006 | B007 | B008 |
---|---|---|---|---|---|---|---|---|
Gender | Male | Male | Male | Male | Male | Male | Male | Male |
Age (years) | 49 | 51 | 59 | 48 | 46 | 67 | 56 | 59 |
AST (IU/L) at baseline | 28 | 44 | 71 | 71 | 26 | 42 | 80 | 19 |
ALT (IU/L) at baseline | 22 | 36.5 | 40 | 48 | 26 | 27.5 | 28 | 13 |
Total bilirubin (μmol/L) at baseline | 8.5 | 43.3 | 18 | 21.7 | 7.5 | 11.1 | 15.3 | 10.1 |
Platelet counts (109/L) at baseline | 230 | 24 | 77 | 173 | 160 | 192 | 276 | 147 |
HBV‐TCRs (HBV‐Env) | HLA‐A0201 | HLA‐A0201 | HLA‐A0201 | HLA‐Cw0801 | HLA‐A0201 | HLA‐A0201 | HLA‐A0201 | HLA‐A0201 |
HBV genotype | C | – | C | C | – | – | – | |
HBsAg serum (IU/ml) | 202 | 1444 | 929.9 | 210.9 | 942.6 | 1549 | 231.5 | 303.8 |
HBeAg status | Negative | Negative | Negative | Negative | Negative | Negative | Negative | Negative |
HBeAb status | Positive | Positive | Positive | Positive | Positive | Positive | Positive | Positive |
Circulating HBV DNA (IU/ml) at baseline | 499 | < 40 | 458 | 991 | < 20 | 44.2 | < 20 | < 20 |
Epitope sequence at baseline | FLLTRILTI | – | FLLTRILTI | FLGPLLVLQA | – | – | – | – |
Circulating HBV DNA (IU/ml) after TCR-T-cell infusions | 30.5 | < 40 | 318 | 492 | < 40 | < 20 | < 20 | < 20 |
Epitope sequence after TCR-T-cell infusions | – | – | FLLTRILTI | FLGPLLVLQA | – | – | – | – |
AFP ≥ 400 ng per milliliter | No | No | No | Yes | No | No | Yes | No |
ECOG performance status score | 1 | 1 | 2 | 2 | 0 | 1 | 1 | 1 |
Child–Pugh classification (score) | A5 | B8 | A6 | B9 | A5 | A6 | A6 | A6 |
BCLC stage | C | B | C | C | C | A | C | C |
Tumor in liver (size, max, cm & number) | Multiple (13.9 × 6.9) | Multiple (3.5 × 1.9) | Multiple (4.8 × 13.1) | Multiple (17.9 × 12.1) | 2 (3.9 × 3.4) | 1 (3.2 × 3.07) | Multiple (11.5 × 9.3) | 2 (3.8 × 3.2) |
Presence of Macrovascular invasion | Yes | No | Yes | Yes | No | No | No | No |
Presence of Extrahepatic spread | Yes | No | Yes | Yes | Yes | No | Yes | Yes |
Antiviral treatment | Entecavir | Entecavir | Entecavir | Entecavir | Entecavir | Entecavir | Entecavir | Entecavir |
Prior treatment for HCC | TACE + Sorafenib | TACE + Sorafenib | RFA | Sorafenib | TACE + Sorafenib | TACE + RFA | Sorafenib | Argon-helium knife therapy for HCC + RFA + Sorafenib |
Combination therapy | Sorafenib | Sorafenib | Sorafenib | Sorafenib | Sorafenib + 1 RFA | 1 Microwave ablation | Sorafenib | Sorafenib |
Therapy after TCR-T-cell infusion | Sorafenib | Sorafenib + Lenvatinib + 2 TACE | Sorafenib | Sorafenib | Sorafenib + 1 RFA | no | Sorafenib | Sorafenib |
Enrollment criteria of patients
Detection of engineered HBV-TCR-T cells
Quantification of circulating HBsAg and HBV DNA
HBV genotype and epitope identification
Statistical analysis
Results
Patient characteristics
Short-term HBV-TCR expression on T cells
Adverse effects
Patients No | The number of infusions and maximum dose | HBV TCR-T cell related AE | Best overall response | TTP (months) | OS (months) | Current status | |
---|---|---|---|---|---|---|---|
AE | Associated dose | ||||||
B001 | 12 (5 × 106/kg) | Grade 3 ALT increase; Grade 3 GGT increase; Grade 3 AST increase; Grade 3 bilirubin increase | 1 × 105/kg | PR | 27.7 | 37.4 (censored) | Loss to follow-up |
B002 | 8 (2 × 106/kg) | Grade 1 ALT increase | 5 × 104/kg | SD | 2.97 | 33.1 | Death |
B003 | 4 (1 × 106/kg) | None | NA | PD | 0.93 | 3.53 | Death |
B004 | 4 (2 × 105/kg) | None | NA | SD | 0.9 | 2.53 | Death |
B005 | 4 (5 × 106/kg) | None | NA | SD | 9.4 | 18.8 (censored) | Loss to follow-up |
B006 | 4 (1.53 × 106/kg) | None | NA | NE | 23.8 | 23.8 (censored) | Alive |
B007 | 8 (5 × 106/kg) | None | NA | PD | 0.2 | 6.7 | Death |
B008 | 8 (5 × 106/kg) | None | NA | NE | 16.9 | 20.0 (censored) | Alive |