Turning the corner on therapeutic cancer vaccines

Therapeutic cancer vaccine target types. Targets for tumor vaccines fall into two general classes: tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs). TAAs are self-antigens that are either preferentially or abnormally expressed in tumor cells, but may be expressed at some level in normal cells as well. As self-antigens, T cells that bind with high affinity to TAAs are typically deleted from the immune repertoire by central and peripheral tolerance mechanisms, and thus a cancer vaccine using these antigens must be potent enough to “break tolerance.” TSAs, comprised of antigens expressed by oncoviruses and neoantigens encoded by cancer mutations, are truly tumor-specific and as such high-affinity T cells may be present and strongly activated by these antigens. Although individual oncoviral antigens are expressed in specific tumor types (e.g., the HPV E6 and E7 antigens in cervical cancer), this occurs in many patients. Similarly, neoantigens encoded by oncogenic driver mutations may be prevalent across patients and tumor types, and hence are referred to as shared neoantigens. The majority of neoantigens are unique to individual patients’ tumors (private neoantigens), and thus require generation of a personalized therap