Table 3.

Summary of representative nano-mRNA therapeutics for targeted cancer immunotherapy under clinical trials.

Targeted immune cells	Nanoformulations	mRNA encoded molecules	Tumor types	Administration routes	Nano-mRNA name	Phase	Status	NCT Number
							(Start year)	(Ref)
Splenic cDCs, pDCs, and macrophages	Lipoplex	Three TAAs	Triple-negative breast cancer	i.v.	BNT114	Phase-I	Active, not recruiting	NCT02316457
							(2016)
As above	Lipoplex	Three TAAs	Ovarian cancer	i.v.	BNT115	Phase-I	Recruiting	NCT04163094
							(2019)
					(W_ova1)
As above	Lipoplex	TAAs	Non-small-cell lung cancer	i.v.	BNT116	Phase-I	Not yet recruiting	NCT05142189
							(Estimated in 2022)
As above	Lipoplex	Kallikrein-2 +Kallikrein-3 +	Metastatic castration-resistant prostate cancer	i.v.	BNT112	Phase-I/II	Recruiting	NCT04382898
		ACP-Prostate + HOXB13 +			(W_pro1)		(2019)
		NK3 homeobox 1
As above	Lipoplex	NY-ESO-1 + MAGE-A3 + TPTE + Tyrosinase	melanoma	i.v.	BNT111	Phase-I/II	Recruiting (2021)/Active, not recruiting (2015)	NCT04526899/NCT02410733
								([23])
Ex vivo human DCs	Protamine	NY-ESO-1 + MAGE-C2 + MUC1	metastatic castration-resistant prostate cancer	i.n.	/	Phase-II	Completed	NCT02692976
								(2015)
								([194])
Skin-APCs	Protamine	NY-ESO-1 + MAGE-C1 + 5T4 +	Non-small-cell lung cancer	i.d.	CV9202	Phase-I/II	Completed (2017)/Terminated (2013)	NCT03164772/NCT01915524
(RNActive®)		MAGE-C2 + Survivin + MUC-1			(BI-1361849)
								([195,196])
As above	Protamine	NY-ESO-1 + MAGE-C1 + 5T4 +	Stage IIIB/IV non-small-cell	i.d.	CV9201	Phase-I/II	Completed	NCT00923312
	(RNActive®)	MAGE-C2 + Survivin	lung cancer				(2009)	([197])
As above	Protamine	Melan-A + Mage-A1 + GP100 +	Stages III/IV metastatic melanoma	i.d.	/	Phase-I/II	Completed	NCT00204607
		Mage-A3 + Survivin + Tyrosinase					(2004)
As above	Protamine	PSA + PSCA + PSMA + STEAP1	Hormone-resistant	i.d.	CV9103	Phase-I/II	Completed	NCT00831467
	(RNActive®)		prostate cancer				(2009)	([198])
As above	Protamine	PSA + PSCA + PSMA + STEAP1 +	High/Intermediate risk	i.d.	CV9104	Phase-II	Terminated	NCT02140138
	(RNActive®)	PAP + Muc1	prostate cancer				(2014)
Splenic cDCs, pDCs, and macrophages	Lipoplex	E6 + E7	HPV16+ head and neck squamous cell carcinoma	i.v./i.d.	BNT113	Phase-I/II	Recruiting (2021)/Recruiting (2017)	NCT04534205/NCT03418480
As above	DOTAP Liposome	Total tumor mRNA +	Pediatric high-grade	i.v.	RNA-LP	Phase-I	Recruiting	NCT04573140
		pp65 full length LAMP mRNA	glioma/glioblastoma				(2021)
dLN-APCs	LNP	Personalised cancer vaccine	Multiple cancers	i.m.	NCI-4650	Phase-I/II	Terminated (2018)	NCT03480152
					(mRNA-4650)			([200])
As above	LNP	As above	Solid tumor/melanoma	i.m	mRNA-4157	Phase-I/II	Recruiting (2017)/Active, not recruiting (2019)	NCT03313778/NCT03897881
As above	Lipopolyplex	As above	Multiple advanced	s.c.	/	Not Applicable	Unknown	NCT03468244
			digestive system cancers				(2018)
APCs	Protamine	As above	Multiple	/	PGV002	Not Applicable	Recruiting	NCT05192460
			digestive system cancers				(Estimated in 2022)
Splenic cDCs, pDCs, and macrophages	Lipoplex	As above	Multiple resected/advanced cancers	i.v.	BNT122	Phase-I/II	Recruiting (2021)/Active, not recruiting (2019)/NCT03815058 (2019)/Withdrawn (2021)/Active, not recruiting (2017)	NCT04486378/NCT04161755/NCT03815058/NCT04267237/NCT03289962
					(RO7198457)
dLN-APCs	LNP	Four KRAS mutated proteins	Multiple KRAS mutant	i.m.	mRNA-5671	Phase-I	Active, not recruiting (2019)	NCT03948763
		(G12D + G12V + G13D + G12C)	advanced/metastatic cancers
Splenic cDCs, pDCs, and macrophages	Lipoplex	CLDN6	Solid Tumor	i.v.	BNT211	Phase-I/II	Recruiting	NCT04503278
							(2020)	([199])
Tumor-T cells, Tumor cells	Cationic polymer/lipid formulation	CD3 × CLDN6 bispecific antibodies	Solid Tumor	i.v.	BNT142	Phase-I/II	Recruiting	NCT05262530
							(2022)
T cells	LNP	Optimized IL-2	Solid Tumor	i.v.	BNT151	Phase-I/II	Recruiting	NCT04455620
							(2021)
As above	LNP	IL-2 + IL-7	Solid Tumor	i.v.	BNT152 + BNT153	Phase-1	Recruiting	NCT04710043
							(2021)
Tumor-T cells, NK cells, macrophages	LNP	IL-12	Advanced Solid tumor	i.t.	MEDI1191	Phase-I	Recruiting	NCT03946800
							(2019)
Tumor - NK cells	LNP	Anti-Claudin 18.2 antibodies	Solid Tumor	i.v.	BNT141	Phase-I/II	Recruiting	NCT04683939
							(2022)
Tumor and TdLN - T cells, macrophages, monocytes, granulocytes, DCs, Tumor cells	LNP	OX40L	Recurrent/refractory solid malignant tumor or lymphoma	i.t.	mRNA-2416	Phase-I	Active, not recruiting	NCT03323398
							(2017)	([201])
As above	LNP	OX40L + IL-23 + IL-36γ	multiple advanced cancers	i.t.	mRNA-2752	Early Phase-I	Recruiting (2018)/Recruiting (2017)	NCT03739931/NCT02872025

Note: i.n.: intranodal injection; TdLN: Tumor draining lymph node.