Table 2 Classification and description of target antigens in TCR-T cell therapy

TAAs

-Endogenous wild-type proteins

Tissue differentiation antigens

• MART-1/Melan-A [34,35,36,37]

• 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 [40,41,42,43,44,45,46,47]

• 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, 64,65,66,67]

• 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 [79,80,81]

• 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