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 |