Cancer targets for ASCI
Several antigens to be included in ASCI are in research and development at GSK, some in collaboration with leading cancer research centers such as the Ludwig Institute.
The first ASCI antigen to be evaluated in a major clinical study (Phase III study) is called MAGE-A3. MAGE-A3 is part of a whole family of MAGE antigens. MAGE-A1 was the first antigen to be identified on a human cancer. It was found in a type of skin cancer called a melanoma and so was named Melanoma AntiGEn-1 (MAGE-1, later renamed MAGE-A1).
The MAGE-A3 protein is an example of a truly cancer-specific antigen that is found in several types of cancer but not on normal cells [Van den Eynde and van der Bruggen, 1997, #51131]. As a result, a single ASCI that targets this antigen has the potential to treat many types of cancer, including Non-Small Cell Lung Cancer (NSCLC), melanoma, breast cancer, head and neck cancer, bladder cancer and liver cancer. Table 1 shows the percentage of patients who express the MAGE-A3 antigen in various types of cancer. These are the patients who could be eligible for treatment by a MAGE-A3 ASCI over the next few years.
Mage-A3 expression in various cancer types
Tumor
|
MAGE-A3 expression
|
| NSCLC |
35-50% |
| Melanoma |
65% |
| Bladder |
62% |
| Esophagus |
47% |
| Head & Neck |
65% |
| Leukemenia |
29% |
| Liver |
48% |
| Ovary |
30% |
| Prostate |
18% |
Results from an initial Phase II study of MAGE-A3 ASCI were presented at an important meeting of cancer specialists – the annual meeting of the American Society of Clinical Oncology (ASCO) in 2007. The results of this study in patients with NSCLC led to the start of a large-scale study. This study has been named MAGRIT– MAGE-A3 as Adjuvant Non-Small Cell Lung Cancer Immunotherapy.
Soon afterwards, a large-scale study of MAGE-A3 ASCI was set up in patients with melanoma. This was based on the results of a Phase II study presented at ASCO in 2008 [Kruit WH et al., 2008, #51131]. The large (Phase III) study in melanoma is called DERMA (aDjuvant immunothERapy with MAGE-A3 in melanomA).
In addition to the MAGE-A3 protein, GSK currently evaluates several other antigens in Phase I and II trials. This could lead to the expansion of ASCI in the future to include even more types of cancer and even more patients affected by each particular type of cancer.