Tumor-Associated Antigens: From Discovery to Immunity

Abstract

There is a renewed enthusiasm for therapeutic vaccination as a viable treatment for patients with cancer. Early tumor vaccines were comprised of whole tumor cells, fragments of tumor cells, or protein lysate from tumor cells. Limited results with these approaches led investigators to begin developing the next generation of cancer vaccines based on defined tumor-associated antigens (TAAs). Defining and characterizing TAAs for human cancer, development of new approaches for identifying TAAs, and novel strategies to deliver the antigens as potent therapeutic vaccines have all been the focus of intense research in the past decade and will continue to be the focus for decades to come.

Overexpressed oncogenic tumor-self antigens

“…This truth led to the TAA discovery movement and the development of various technologies for its accomplishment. 6 This produced many candidate vaccine antigens that with further effort, could yield ideal targets for the next generation of cancer vaccines, among them being the overexpressed tumor-self antigens. This large group of understudied vaccine targets represents (as the name implies) self proteins with limited or low but detectable expression in many normal healthy cells and tissues and overexpression in multiple to most cancers.…”

“…Examples include, viral proteins specifically associated with virus-induced malignancies (approximately 12% of all cancers), 12 and oncogene and tumor suppressor gene products or their mutant variants. 6 Oncofetal antigens and melanoma associated antigens represent those with restricted expression in non-malignant tissues, 13,14 whereas cancer testis antigens are only expressed, as the name suggests, in the tumor and in testes, with testes being protected by mechanisms of immune privilege. 15 Overexpressed antigens are a large and diverse group that includes any protein found at increased levels in tumors compared with normal healthy cells and tissues.…”

“…While passive immunotherapies often engage the immune system independent of the knowledge of defined tumor antigens (an exception being some forms of adoptive cell therapy 5 ), vaccines elicit specific immune responses by targeting defined tumor antigens. 6 With the exception of vaccines to prevent cervical cancer by targeting select serotypes of human papillomaviruses, 7 most if not all vaccine clinical trials have focused on therapy. In this approach the vaccine is administered when tumors are present in the patient, with the primary goal of shrinking the tumor mass.…”

Glycans as Biomarkers: Status and Perspectives

“…During malignant transformation, blood group antigens can be increased, decreased or have aberrant structures, whereas some tumors can express histoblood groups which are not compatible with the erythrocytic blood group due to aberrant synthesis by blood-group-dependent glycosyltransferases (11,19,39,40). These carbohydrate antigens can be added to different substrates: N-glycans, O-glycans and glycosphy ngolipids.…”

The role of the inflammatory microenvironment in thyroid carcinogenesis

“…Tumor-associated antigens comprise gene products more frequently found in tumors, whereas tumor-specific antigens are gene products uniquely expressed in tumors (Lewis et al 2003). These groups of antigens are target for immunotherapy, and new targets have actively been searched for all over the world.…”