Table 1.
Currently reported TCR gene transfer attempts for hematological malignancies.
| Target antigen | HLA restriction | vector | Comments | Transduction efficacy | Reference |
|---|---|---|---|---|---|
| WT1 | HLA-A*0201 | retroviral vector | WT1-specific TCR gene was transduced into PBL. CD8+ or CD4+ T cells could exert target specificity. | 40~60% in total T cells by Vb2 Ab after 2 rounds of antigen-specific stimulation | [8] |
| HLA-A*0201 | optimized retroviral vector | WT1-specific TCR gene was modified to express more efficiently (hybrid human-murine TCR, Cys-mutant TCR). Patients' PBL transduced WT1-specific TCR could reject the engraftment of autologous CML-BC cells in NOD/SCID mice model. | conventional vector: 0.6% in total CD8+ T cells by tetramer (nonstimulated) optimised vector: 6% in total CD8+ T cells by tetramer (nonstimulated) | [26, 27] | |
| HLA-A*2402 | lentiviral vector | WT1-specific TCR gene was transduced into PBL. CD8+ or CD4+ T cells could exert target specificity in an HLA class I-restricted fashion. | 60% in total T cells by Vb5.1 Ab (nonstimulated) 20% in sorted CD8+ T cells by tetramer | [11] | |
| HLA-A*2402 | optimized retroviral vector | The vector could suppress endogenous TCR by shRNA and increase transduced codon-optimized TCR simultaneously. | 44% in transduced CD8+ T cells by tetramer | [28] | |
| HA-1 | HLA-A*0201 | retroviral vector | HA-1-specific TCR gene was transduced into T cells. These transfectants could exert target specificity. | 6.6% in transduced T cells by tetrameter | [9] |
| HA-2 | HLA-A*0201 | retroviral vector | HA-2-specific TCR gene transduced CD8+ T cell clone was established. These transfectants could exert target specificity. | NA | [10] |
| HLA-A*0201 | retroviral vector | HA-2-specific TCR gene was transduced into CMV-specific CTL clone to exploit the viral specific response in vivo for the long-term persistence of target TCR transfectants. | NA | [29] |
Abbreviations: WT1, Wilms' tumor gene product 1; PBL, peripheral blood lymphocytes; CML-BC, chronic myelogenous leukemia-blastic crisis; CMV, cytomegalovirus; NA, not available; Ab, antibody.