Review Article

Application of Adoptive T-Cell Therapy Using Tumor Antigen-Specific T-Cell Receptor Gene Transfer for the Treatment of Human Leukemia

Table 1

Currently reported TCR gene transfer attempts for hematological malignancies.

Target antigenHLA restrictionvectorCommentsTransduction efficacyReference

WT1HLA-A*0201retroviral vectorWT1-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*0201optimized retroviral vectorWT1-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*2402lentiviral vectorWT1-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*2402optimized retroviral vectorThe vector could suppress endogenous TCR by shRNA and increase transduced codon-optimized TCR simultaneously.44% in transduced CD8+ T cells by tetramer[28]
HA-1HLA-A*0201retroviral vectorHA-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-2HLA-A*0201retroviral vectorHA-2-specific TCR gene transduced CD8+ T cell clone was established. These transfectants could exert target specificity.NA[10]
HLA-A*0201retroviral vectorHA-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.