Table I.

Targeting of Tumor-Associated Antigens in T-cell Immunotherapy

Class	Advantages	Concerns	Examples
Tissue differentiation antigens	Shared antigens “Off the shelf” treatments can be developed	Expression on normal tissues Potential for on-target, off-tumor toxicity	MART-1 gp100 CEA CD19
Tumor germline (“tumor-testis”) antigens	Shared antigens “Off the shelf” treatments can be developed Potentially tumor-specific	Potential for on-target, off-tumor toxicity May be expressed in a low frequency of cancers	NY-ESO1 MAGE-A3
Normal proteins overexpressed by cancer cells	Shared antigens “Off the shelf” treatments can be developed	On-target, off-tumor toxicity	hTERT EGFR mesothelin
Viral proteins*	Shared antigens “Off the shelf” treatments can be developed Tumor specific, thus minimal risk of on-target, off-tumor toxicity	Low frequency of virus-associated cancers	HPV EBV MCC
Tumor-specific mutated antigens	Tumor specific, thus minimal risk of on-target, off-tumor toxicity Shared driver/hot-spot mutations can potentially be targeted	Currently requires surgical resection for next-generation sequencing Most immunogenic mutations identified so far are patient-specific Extended time to develop personalized treatment targeting mutations	Mum-1 B-catenin CDK4 ERBB2IP

^*Not included in this review