Tumor antigens consist of TSTAs, TATAs and Oncogene proteins. Tumor-specific antigens have been identified on tumors induced by chemical and physical carcinogens and some virally induced tumors.
Vaccine approaches have focused on shared tumor antigens. This is primarily due to MHC polymorphism as well as the fact that not all tumors of a given type express the same antigens. Virus-associated tumors cause 15% of all human cancers. They have the benefit of most if not all of the tumor cells expressing the same viral antigen.
Currently researchers have discovered a peptide encoded by Human Papiloma Virus associated with cervical cancer. Studies are being conducted to determine if pre-exposure to the peptide will induce an immune response which when later challenged with the cancer cells will result in rejection of the cancer. This is the basis of all vaccine development.
An antigen called Globo H, found in high numbers on the surface of many cancer cells, including prostrate and breast cancer, is currently under investigation in phase I trials. Globo H is attached to a carrier protein called KLH in order for the human immune system to recognize it as foreign. The pre-clinical trial has shown that this vaccine is able to induce production of antibodies to tumor cells which display high levels of the antigen.
On a similar note, several mutated oncogenes have been found which can serve as tumor specific antigens. Specific mutations in the Ras proto-oncogene are present in approximately 25% of human cancers. In experiments undertaken by Jung & Schluesener, CD4+ T cell-lines were established that specifically recognized the mutated Ras oncogene. However, as is the case with the many potential target oncogenes discovered, their ability to illicit a protective immune response is dependent on numerous factors such as their frequency, homogeneity and specificity in any given tumor tissue. In addition the extent of their binding to MHC I molecules of the host must be taken into consideration. Phase I & II clinical trials of Ras peptide cancer genes are currently underway.
A promising finding is that breast cancer cells exhibit increased expression of the oncogene encoded Neu protein compared to normal cells which display only trace amounts. This finding suggests that Neu monoclonal antibodies can recognize and selectively eliminate breast cancer cells with out a substantial amount of damage to normal cells. Phase I trials are under investigation to study the effectiveness of use of Neu vaccine with Granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant in patients with breast and ovarian cancer.