Table 1.

Categories of tumor antigens

Category	Normal tissue expression	Expression levels in normal tissues	Examples	Advantages of targeting antigens	Disadvantages of targeting antigens
Over-expressed gene products	Broadly distributed	Low	PRAME	Expressed in a wide variety of cancer types	Potential for autoimmunity due to broad normal-tissue expression
Tissue-specific differentiation antigens	Narrow: single tissues	Generally high	MART-1, CEA	Many products expressed at high levels in one or limited number of tissues	Autoimmunity can limit the ability to develop potent therapies
Cancer germline antigens	Germ cells	Generally high	MAGE-A family, NY-ESO-1	Generally not expressed in normal adult tissues with the exception of germ cells	Some family members are expressed in adult normal tissues, leading to autoimmunity
Viral antigens	None	None	HPV E6, HPV E7	Not expressed in any normal tissues	The number of therapeutic targets may be limited by mechanisms of viral immune evasion
Mutated antigens	None	None	KRASG12D, KRASG12V	Not expressed in any normal tissues. Some hotspot mutations are present at relatively high frequencies in particular tumor types. Targeting hotspot mutations may help to obviate antigen loss	Many are limited to one, or a small number of, tumors