Table 3.
Representative in vitro differentiation methods of generating iPSC-derived T cells for cancer cell therapy.
| Publications | Final Products (Immune Cell Types) |
Start Material | iPSC Genetic Modification | Feeder or Feeder-Free | Overall Procedure Time | Major Components in Culture Medium |
|---|---|---|---|---|---|---|
| Nishimura et al., 2013 [49] | Conventional αβ T cells | CD3+ PBMC T cells for a healthy donor; HIV-1-specific CD8+ T cells |
NA | Feeder: C3H10T1/2, OP9-DL1 | 33–40 days | VEGF, SCF, FLT-3L, IL-7, IL-15 |
| Themeli et al., 2013 [50] | Conventional αβ T cells | Peripheral blood T lymphocytes (PBL) from a healthy donor | 19CAR-engineering | Half feeder-free; Half feeder: OP9-DLL1 | ~30 days | BMP-4, FGF, VEGF, SCF, FLT-3L, IL-3, IL-7 |
| Vizcardo et al., 2013 [48] | Conventional αβ T cells | JKF6 cells (MART-1 specific TILs) | NA | Feeder: OP9, OP9-DLL1 | ~40 days | SCF, FLT-3L, IL-7, IL-2 |
| Maeda et al., 2016 [65] | Conventional αβ T cells | LMP2-specific CTLs from a healthy donor | NA | Feeder: OP9, OP9-DLL1 | ~6–8 weeks | IL-7, FLT-3L, SCF, IL-2, IL-21 |
| Minagawa et al., 2018 [66] | Conventional αβ T cells | GPC3-specific CTLs from GPC3 peptide-vaccinated patients; Monocyte-derived HLA-typed iPSCs |
RAG2 knockout; WT1-TCR transduction |
Feeder: C3H10T1/2, OP9-DLL1 | NA | FGF, VEGF, SCF, IL-7, FLT-3L, IL-15, |
| Maeda et al., 2020 [63] | Conventional αβ T cells | Monocytes derived iPSCs from the HLA-homo donor | WT1-TCR transduction | Feeder: OP9, OP9-DLL1 | ~36 days | FGF, IL-7, FLT-3L, SCF, IL-7, IL-21 |
| Iriguchi et al., 2021 [67] | Conventional αβ T cells | Peripheral blood T cells; HIV-1-specific CTLs; RAG2-deleted GPC3 T-iPSCs | NA | Feeder-free | ~42 days | CHIR99021, BMP4, FGF, VEGF, SCF, TPO, FLT-3L, SDF1α |
| Trotman-Grant et al., 2021 [68] | Conventional αβ T cells | Human IPS11- and STIPS cell lines | NA | Feeder-free | ~42 days | BMP4, FGF, VEGF, FLT-3L, SCF, IL-7 |
| Wang et al., 2021 [51] | Conventional αβ T cells | Human iPSC line: GPC3-16-1 (generated from CTLs) | PVR knockout; HLA-E transduction; B2M knockout; CIITA knockout | Feeder: OP9-DLL1 | NA | CHIR99201, FGF, VEGF, BMP4, SCF, FLT-3L, TPO, IL-7, IL-15 |
| Wang et al., 2022 [69] | Conventional αβ T cells | iPSC clones from CD62L+ T cells | 19CAR-engineering | Feeder: MS5-DLL4 | ~51–64 days | BMP4, VEGF, FGF, EGM-2, SB-431542, SCF, FLT3, IL-7, TPO, IL-2, IL-7 |
LMP2: Latent membrane protein 2; CTLs: cytotoxic T lymphocytes; GPC3: Glypican 3; RAG2: recombinase-activating-gene-2; NA: not available.