Abbott is expanding its existing agreement with GlaxoSmithKline (GSK) Biologicals to include the development of an additional companion diagnostic in support of GSK's cancer immunotherapy research program. Abbott will develop a PCR test for use on the Abbott m2000rt™ instrument to screen non-small-cell lung cancer (NSCLC) tumors for the expression of the PRAME antigen.
PRAME is a preferentially expressed antigen of melanoma that is found in 69% of NSCLC cases as well as in other cancers like melanoma and breast, ovarian, and bladder cancers, with limited expression in normal cells, according to the firms.
The existing agreements between the two companies, announced in July 2009 and March 2010, focused on the development of PCR tests to screen NSCLC and melanoma tumors for expression of the MAGE-A3 antigen.
MAGE-A3 is a tumor-specific antigen that is expressed in a variety of cancers including melanoma and non-small-cell lung, head and neck, and bladder cancers, with no expression in normal cells. Expression of the MAGE-A3 gene has been observed in testicular cells but without antigen presentation capabilities.
MAGE-A3 protein has been in-licensed by GSK from the Ludwig Institute for Cancer Research.
GSK explains that its antigen-specific cancer immunotherapy (ASCI) program represents a class of medicines designed to train the immune system to recognize and eliminate cancer cells in a highly specific manner. These immunotherapeutics combine tumor antigens, delivered as purified recombinant proteins, and GSK's adjuvant systems, which are specific combinations of immunostimulating compounds selected to increase the antitumor immune response.
ASCIs are being investigated in the clinic to support their use to reduce the risk of tumor recurrence following surgery or to impact tumor growth in an early metastatic setting. Besides PRAME and MAGE-A3, the ASCI program is also targeting NY-ESO-1 for the treatment of metastatic melanoma and WT1 for acute myelogenous leukemia. GSK’s lead candidate is in Phase III studies as a treatment for NSCLC.
GSK notes that the highly specific mode of action of its ASCIs allows development of diagnostic tools to aid in selecting patients eligible for the treatment, depending on the expression of the tumor antigens. Stafford O'Kelly, head of Abbott's molecular diagnostics business, says, "This expanded collaboration, along with Abbott's other recently announced partnerships in oncology, demonstrates the continued commitment Abbott is making to assess biomarkers linked to immunotherapies in various cancers."
This August Abbott received FDA approval for a test designed to detect rearrangements of the anaplastic lymphoma kinase (ALK) gene in NSCLC. The Abbott Vysis ALK Break Apart FISH Probe test is designed to identify ALK-positive NSCLC patients for Pfizer’s approved NSCLC therapy, Xalkori, an oral ALK inhibitor. In May it said it had filed a premarket approval application in Japan for this companion diagnostic. Abbott began working with Pfizer in August 2009.