Table 2.

Classification and description of target antigens in TCR-T cell therapy

Categories		Shared antigens and genes in solid tumors	Advantages	Disadvantages
TAAs -Endogenous wild-type proteins	Tissue differentiation antigens	• MART-1/Melan-A [34–37] • gp100 [35] TYRP1[38] • mesothelin [39]	Antigen ubiquity: widely shared between patients; widely shared under tumor heterogeneity Easier to recognize, isolate and validate Relatively mature, have undergone clinical tests	Prone to immune evasion under affinity limitation Relatively poor effect, easily tolerated Autosomal cross-reactions have been widely reported, causing multiple injuries and even death
	Cancer germline antigens	• NY-ESO-1 [40–47] • MAGE-A [48-53] • BAGE [54] • SAGE [55] • HAGE [56] [57] • SSX [58] • LAGE [59] • SCP1 [60] • PRAME[61]
TSAs (neoantigens) -Somatic mutant proteins	Neoantigens from genomic mutations: SNVs; Indels; Fusion genes; Chromosomal structural abnormalities	SNVs • TP53 [21, 62, 63] • KRAS [22, 64–67] • IDH1 [68] • JAK2 [69] • BRAF [70] • CDK4 [71] • CDK12 [72] • NRAS [65] • CTNNB1 [73] • GAS7 [74] Indels • NPM1 [75] • CALR [76] • TGFBR2 [77] Fusion genes • BRD4-NUT [78] • NTRK1/2/3 [79–81] • NRG1 [82]	No expression in normal somatic cells No T cell thymocyte selection and central immune tolerance Individuation, more in line with the heterogeneity of patients with tumors, new therapeutic potential	Need to predict and characterize, more cost of time and resources Need to find commonality Immature and difficult to validate Unknown risk of cross-reactivity
	Viral neoantigens (viral open reading frames)	• HPV-16 E7 • HPV-16 E6
	Neoantigens of transcriptomic variants	• COL6A3-FLNV [83]
	Neoantigens of proteomic variation/ abnormal antigenic peptide presentation	• LUAD [84]
MiHAs	A large antigen library distinct from MHC presentation		Available applications in hematologic malignancies	Strict requirement of individual matching

TAA tumor-associated antigen, TSA tumor-specific antigen, MiHA minor histocompatibility antigen, SNV single nucleotide variation