Table 2.
Summary of conventional drugs with new uses in CAR-T cells
| Drugs | Function | Conventional use | New use for T/CAR-T |
|---|---|---|---|
| GDC-0941 [108] | PI3Kδ inhibitor |
Inhibiting breast cancer growth Combined with radiotherapy in glioblastoma |
Enhances the proliferative potential, function, and survival of CD8+ T cells |
| Idelalisib [109] | PI3Kδ inhibitor |
Relapsed chronic lymphocytic leukemia Relapsed follicular B-cell non-Hodgkin lymphoma Relapsed small lymphocytic lymphoma |
Enriches the less-differentiated naïve-like T cells and decreases the expression of the exhaustion markers PD-1 and Tim-3 |
| Duvelisib [110] | PI3Kδ/γ inhibitor |
Chronic lymphocytic leukemia Small lymphocytic lymphoma |
Normalizes the CD4/CD8 ratio and maximizes the number of CD8 + T-stem cell memory, naïve, and central memory T cells |
| Ibrutinib [111] | BTK/ITK inhibitor | Chronic lymphocytic leukemia | Enriches CART cells with a less-differentiated naïve-like phenotype and decreases expression of exhaustion markers |
| LY294002 [112] | PI3Kα/δ/β inhibitor | Reversing gemcitabine resistance in pancreatic cancer | Suppresses effector differentiation and increases TN and TCM cell proportions without diminishing therapeutic T cell expansion |
| Rapamycin [113] | mTOR inhibitor | Attenuating GvHD in clinical trial | Enhances the infiltration capacity of EpCAM CAR-T cells into bone marrow |
| Decitabine [37] | DNA methylation inhibitor | Treatment for myelodysplastic syndrome | Increases expression of memory-related genes, strengthens proliferation potency, cytokine production, and confers a stronger tumor lytic capacity to tumor cells |
| SAHA [114] | HDAC inhibitor | Treatment for cutaneous T cell lymphoma | Reduces expression of immunosuppressive molecules (e.g., CTLA-4, TET2) in B7-H3 CAR-T cells |
| JQ1 [115] | BET inhibitor | Treatment for castration-resistant prostate cancer | Inhibits BET protein BRD4 directly and regulates expression of the transcription factor BATF in CD8+ T cells |
| Sulforaphane [116] |
HDAC inhibitor; Nrf2 activator |
Treatment for autism spectrum disorder | Pretreatment downregulates PD-1 expression in meso CAR-T cells by inhibiting the PI3K-AKT pathway |
| Metformin [92] | AMPK activator | Treatment for type II diabetes | Reprograms the differentiation of T cells and maintains the phenotype and function of TSCM and TCM cells through the AMPK-miRNA-EOMES-PD1 pathway |
| Auranofin [117] | NRF2 activator; TrxR inhibitor |
Treatment for rheumatoid arthritis; Treatment for triple-negative breast cancer |
Increases elimination of CD19+ tumor cells or autologous tumor spheroids |