Table 1.
Summary of small-molecule drugs enhancing adoptive T cells ex vivo.
| Compound | Names | Target | T Cell Product | Tumor Model | CRS |
|---|---|---|---|---|---|
| Protein Kinase Inhibitors | |||||
| GDC-0941 | Pictilisib | pan-PI3K | gp100-TCR (16) | Melanoma | |
| LY294002 | PI3K α/δ/β | CD33-CAR (17) | AML | ||
| CAL-101 | Idelalisib | PI3K δ | gp100-TCR (18) CD19-CAR (19, 20) CD5-CAR (21) Meso-CAR (22) |
Melanoma CLL DLBCL Melanoma |
|
| IPI-145 | Duvelisib | PI3K δ/γ | gp100-TCR (22) Meso-CAR (22) CD19-CAR (20) |
Melanoma CLL |
Lower (23) |
| IPI-549 | Eganelisib | PI3K γ | gp100-TCR (22) Meso-CAR (22) |
Melanoma | |
| TGR-1202 | Umbralisib | PI3K δ | gp100-TCR (22) Meso-CAR (22) |
Melanoma | |
| bb007 | PI3K | BCMA-CAR (24) | MM | ||
| Rapamycin | Sirolimus | mTORC1 | EpCAM-CAR (25) | AML | |
| Akt inhibitor VIII | Akt | TIL (26) gp100-TCR (26) CD19-CAR (27, 28) MiHA-specific (29) |
Melanoma Melanoma ALL |
||
| GDC-0068 | Ipatasertib | Akt | MiHA-specific (29) | ||
| MK2206 | Akt | EpCAM-CAR (30) | Colon Cancer | ||
| Ibrutinib | BTK | CD19-CAR (31–36) | CLL, NHL, ALL | Lower (33) | |
| Acalanrutinib | BTK | CD19-CAR (36) | ALL | ||
| Zanubritinib | BTK | CD19-CAR (37) | B-malignancy | ||
| Dasatinib | TK | CD19-CAR (38) | ALL | ||
| Epigenetic modulators | |||||
| Decitabine | DNMT | CD19-CAR (39) CD20-CAR (39) NY-ESO-1-TCR (40) |
ALL ALL AML |
||
| Panobinostat | HDAC | Her2-CAR (41) gp100-TCR (41) |
PDAC PDAC |
||
| SAHA | HDAC | B7-H3-CAR (42) | TNBC, HNSCC | ||
| Sulforaphane | HDAC | Meso-CAR (43) | Lung Cancer | ||
| JQ1 | BRD4 | CD19-CAR (44, 45) HLA-A2/MART127-35-TCR (44) |
ALL Melanoma |
||
| Immunomodulators | |||||
| Lenalidomide | Myeloma-specific (46) CS1-CAR (47) BCMA-CAR (48) CD23-CAR (49) WT1-CAR (50) CD133-CAR (51) HER2-CAR (51) EGFRvIII-CAR (52) CD19-CAR (53) |
MM MM MM CLL Wilms Tumor Glioma Breast Cancer GBM DLBCL |
|||
| Peptide-based modulators | |||||
| VIPhyb | VPAC1/2 | CD5 (21) TMV-cultured |
DLBCL Colon Cancer |
||
| ANT308 | VPAC1/2 | T cells | |||
AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; NHL, non-Hodgkin’s lymphoma; PDAC, pancreatic ductal adenocarcinoma; TNBC, triple negative breast cancer; HNSCC, head and neck squamous cell carcinoma; MM, multiple myeloma; GBM, glioblastoma.