Protein Predicts Survival in Breast Cancer Patients

There is evidence that an immune filtrate exists in breast cancers, indicating that immunotherapy may succeed in targeted patients, particularly those with regional or minimal residual disease. High serum levels of LAG-3 protein (sLAG-3), as a Th1 marker, are associated with resistance to tuberculosis in a large series of patients. Researchers decided to test whether, if cell-mediated immune mechanisms are important for improved prognosis, high levels of sLAG-3 are correlated with improved survival in subsets of breast cancer patients.

The study was conducted by Dr. Marie-France Pichon and Kamel Hacene of the René Huguenin Cancer Center (Saint-Cloud, France), and Professor Frédéric Triebel, now scientific and medical director of Immutep S.A. (Châtenay-Malabry, France). The study was published in the April 8, 2006, issue of Cancer Letters.

Studying a cohort of 246 breast patients' sera collected in 1994 at time of first diagnosis, the researchers found that both disease-free and overall survival rates were greater in patients with estrogen or progesterone receptor-positive tumor cells who had detectable levels of sLAG-3 at diagnosis, versus patients with undetectable sLAG-3 levels. These results indicate that sLAG-3 may be a valuable marker for prognosis in some subsets of breast cancers and, more importantly, that cell-mediated mechanisms such as Th1 responses do have an impact on survival, a pre-requisite for setting-up immunotherapy protocols as a form of adjuvant therapy for breast cancer.

"It is striking that whatever the stage of the disease in 1994 and the type of subsequent therapy, we were able to show that high levels of sLAG-3 in the ng/ml range in the sera collected at diagnosis are associated with a much better outcome 10 years later,” said Frédéric Triebel. "These results have encouraged us to mimic nature's work by directly injecting in patients a recombinant sLAG-3 protein, termed IMP321, without any tumor antigen, as a first line therapy in mostly incurable diseases such as metastatic renal cell or breast carcinomas.”



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