Table 1.

Review of current research on CAR-NK combination drugs against various solid tumors.

Serial NO.	Tumor Type and cell lines	Specific Target	Source of NK cells	CAR composition	Drug Category	Examples	Advantages	References PMID
1	Castration‐resistant prostate cancer	PMSA	NK-92	NKG2D-2B4-CD3ζ	Immune checkpoint inhibitors	Anti‐PD‐L1 mAb; Atezolizumab	Anti‐PD‐L1 mAb significantly enhanced the anti-tumour effect of CAR NK‐92 cells.	35696531
2	Cisplatin-resistant lung cancer	N	NK-92MI，primary NK	N	Immune checkpoint inhibitors	Anti-PD-1, anti-PD-L1, MEK/Erk pathway inhibitors	Enhance NK cell cytotoxicity to cisplatin-resistant cells.	28801607
3	K562 myeloid leukemia cells	N	PBMC	N	Immune checkpoint inhibitors	Atezolizumab	Anti-PD-L1 mAb augments human PD-L1+ NK cell antitumor activity in vivo	31340937
4	Multiple myeloma (MM) cells	N	NK, PBMC	N	Immune checkpoint inhibitors	anti-PD-1 mAb	PD-1 blocking enhanced exNK cell degranulation and cytolytic activity.	27356741
5	MDA-MB-231、H460 and HTB1	PD-L1	high- affinity natural killer (t- haNK)，NK-92	Not detailed.	Immune checkpoint inhibitors	anti- PD-1, N-803 (IL-15 superagonist)	These studies demonstrate the antitumor efficacy of PD-L1 thaNK cells and provide a rationale for the potential use of these cells in clinical studies.	32439799
6	Digestive cancers	N	NK-92, NKL	N	Immune checkpoint inhibitors	Anti-PD-1, anti-PD-L1	Blocking PD-1/PD-L1 signaling markedly enhances cytokines production and degranulation and suppresses apoptosis of NK cells in vitro.	28692048
7	Head and neck cancer	N	PBMC	N	Immune checkpoint inhibitors	Nivolumab，Cetuximab	PD-1 blockade on NK cells enhances cetuximab mediated ADCC of PD-L1high tumor cells.	30282672
8	Hematopoietic tumor	N	Primary,NK-92	N	Immune checkpoint inhibitors	anti-PD-L1 mAb	Blocking PD-L1 increases susceptibility to NK cell killing.	26155422
9	Ovarian cancer	N	PM21-NK, PBMC	N	Immune checkpoint inhibitors	anti-PD-L1	PD-L1 blockade enhances anti-tumor efficacy of NK cells.	30377572
10	PD-L1- positive cancer cell lines	N	NK-92-CD16， PBMC	N	Immune checkpoint inhibitors	Atezolizumab， An anti- hPD- L1- hIgG1	NK cells induce an ADCC response in combination with anti- PD-L1 mAbs, which helps promote ADCC antitumor activity against PD-L1- positive tumors.	32830112
11	K562	N	NK-92	N	Immune checkpoint inhibitors	Anti-PD-1, anti-PD-L1	PD-1 and PD-L1 blockade elicited a strong NK cell response that was indispensable for the full therapeutic effect of immunotherapy.	30198904
12	Cisplatin resistant ovarian cancer	N	NK-92MI	N	Chemotherapy	Cisplatin	Overcome immunoresistance of chemoresistant ovarian cancers.	34058473
13	Ovarian cancer	CD44	NK-92	CD28−CD28-4-1BB-CD3ζ	Chemotherapy	Cisplatin	The simultaneous treatment with CD44NK and cisplatin showed higher anti-tumor activity than sequential treatment.	34680456
14	Gastric cancer	NKG2D	PBMC	4-1BB- CD3ζ	Chemotherapy	Cisplatin	Enhance cytototoxicity.	30132099
15	Ovarian cancer	CD133	NK-92	CD28−CD28-4-1BB-CD3ζ	Chemotherapy	Cisplatin	The sequential treatment with cisplatin followed by CAR-NK cells led to the strongest killing effect.	28836469
16	Pancreatic Carcinoma	Robo1	NK-92	N	Radiotherapy	125I Seed Brachytherapy	Robo1 specific CAR-NK immunotherapy enhances efficacy of 125I seed brachytherapy in an orthotopic pancreatic cancer mouse model.	31704816
17	Colorectal Cancer	EpCAM	NK-92	CD8-4-1BB-CD3ζ	Tyrosine-kinase inhibitor	Regorafenib	Enhance the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.	30410941
18	Hepatocellular Carcinoma	GPC3	PBMC	CD8−CD28−CD3ζ	Tyrosine-kinase inhibitor	Sorafenib	The upregulated tumor cell apoptosis induced by the combined treatment.	31078430
19	Renal Cell Carcinoma (RCC)	EGFR	NK-92	CD8−CD28−CD137-CD3ζ	Tyrosine kinase inhibitor	Cabozantinib	Enhance the killing ability of CAR-NK-92 cells against the RCC cells.	29423418
20	Advanced renal cell carcinoma	CAIX	NK-92	CD8−CD28-4-1BB- CD3ζ	Proteasome inhibitor	Bortezomib	Bortezomib can enhance the effects of the CAR-NK92 cells against RCC in vitro and in vivo.	30272343
21	Pancreatic cancer	Mesothelin	NK-92	CD8-4-1BB-CD3ζ	STING agonists	Cyclic GMP-AMP (cGAMP)	Combination of CAR-NK-92 cells targeting mesothelin and cGAMP displayed greater antitumor efficacy.	35371622
22	Hematologic malignancies and solid tumors	CD16a	Human iPSCs	N	Antibodybased drugs	anti-CD20 mAb, anti-HER2 mAb	HnCD16-iNK cells combined with mAbs are highly effective against hematologic malignancies and solid tumors that are typically resistant to NK cell–mediated killing.	31856277
23	Glioblastoma	EGFR	PBMCs	N	Oncolytic virus	An oncolytic virus expressing IL-15/IL-15Rα	OV-IL15C plus EGFR-CAR NK cells synergistically suppressed tumor growth and significantly improved survival.	34006525
24	lung cancer	B7–H3	NK-92MI	N	Photothermal Therapy (PTT)	Near infrared (NIR-II)	synergistic CAR-NK immunotherapy is carried out specifically to eradicate any possible residual tumor cells after PTT.	34159726
25	Human Pancreatic Carcinoma	Robo1	Primary NK cells	N	Brachytherapy	Iodine 125 seed brachytherap-y (125I IBT)	Robo1 specific CAR-NK immunotherapy enhances efficacy of125I IBT in an orthotopic pancreatic cancer mouse model.	31704816

Data were obtained from the PubMed database. N-denotes information not provided in the study. Other abbreviations: iPSC, induced pluripotent stem cell. PBMCs, Peripheral Blood Mononuclear Cells.