Table 1.

Preclinical research on CAR-T combination therapy

Target	Combination therapy	Type of disease	Time	Mechanism	Refs
CD19	PI3K inhibitors	CLL	2022	i. Inhibit PI3K-mediated cell apoptosis by blocking Fas signal transduction. ii. Suppress cellular exhaustion. iii .Increasing the expression of mitochondrial fusion protein MFN2.	[44]
CD19	venetoclax	R/R NHL	2022	Enhance CAR-T cell cytotoxicity.	[45]
BCMA	GSI	MM	2019	Inhibit BCMA degradation.	[46]
CS1	lenalidomide	MM	2018	i.Increase the proportion of CD8 + CAR-T cells and decrease the proportion of CD4 + CAR-T cells. ii.Promote Th1 cytokine expression in CAR-T cells and inhibit Th2 cytokines. iii.Lenalidomide improves the formation of immune synapses between CAR-T cells and tumor cells, enhancing cytotoxicity against tumor cells.	[47]
CD19	lenalidomide	DLBCL	2023	i.Polarize CD8 + CAR-T cells into CD8 + central memory cells and Th1 type. ii.Delay CAR-T exhaustion. iii.Promote CAR-T cell expansion.	[48]
BCMA	lenalidomide	MM	2019	i.Alter Th1 cell response, T cell activation, cytokine production, cell cycle control, and cytoskeletal remodeling-associated pathways. ii.In murine models, increased the number of circulating CAR-T cells in the bloodstream.	[49]

PI3K: Phosphatidylinositol 3-Kinase; CLL: chronic lymphocytic leukemia; R/R NHL: Relapsed/Refractory non-Hodgkin lymphoma; BCMA: B-cell maturation antigen; GSI: γ-secretase inhibitors; MM: multiple myeloma; DLBCL: diffuse large B-cell lymphoma