Kristi A Egland Lab
Behind the research
Early and personalized diagnosis for breast cancer patients is crucial for optimizing treatments leading to long-term survival. It has been previously shown that cancer proteins can elicit an immune response in patients. These autoantibodies recognize tumor-associated antigens (TAA), autologous cellular proteins that are mutated, modified or aberrantly expressed in tumor cells. Because anti-TAA antibodies reflect and amplify the cellular changes associated with tumorigenesis, detection of anti-TAA antibodies in the sera of breast cancer patients may provide a non-invasive mechanism for the early detection of breast cancer.
Dr. Egland’s lab took a molecular approach to identify potential tumor antigens that elicit an antibody response in breast cancer patients by generating a cDNA library (MAPcL) enriched with genes encoding membrane and secreted proteins, which are more likely to induce an antibody response in patients compared to intracellular proteins. Her lab has established an expression strategy to generate MAPcL Fc-fusion proteins that retain their native conformation and are efficiently recognized by patients’ antibodies.
The long-term goal of Dr. Egland’s lab is to develop a blood test for breast cancer based on detecting a patient’s antibodies generated against cancer proteins. In addition, the team has selected previously uncharacterized MAPcL genes that encode proteins overexpressed in breast cancers but have restricted expression in the normal essential organs, and are characterizing the role of these MAPcL proteins in breast tumorigenesis.
It is well established that breast cancer patients often produce antibodies to cancer cells. Cancer cells can have proteins that are present in much higher levels than in normal cells, and the immune system can sense these abnormal tumor proteins. Because it is equipped with an amplification system, the immune system can produce large amounts of antibodies to the abnormal proteins, even when the change in tumor proteins is too small to be detected by current diagnostic tests. Therefore, by detecting the presence of antibodies to a particular tumor antigen, rather than tumor antigen itself, we can achieve high sensitivity allowing earlier diagnosis.
Recently, the Dr. Egland’s lab isolated a collection of genes, called a library, encoding membrane and secreted proteins from breast cancer cells. Subsequently, the genes in this library that were ubiquitously expressed in normal essential tissues were removed. In order to determine what genes are represented in this library, the team obtained DNA sequences of 25,277 of the genes. Secreted and membrane proteins are more likely to induce an antibody response than intracellular proteins. Therefore, this library of clones encoding membrane and secreted tumor antigens is enriched with genes encoding proteins that should preferentially induce an antibody response in patients.
Dr. Egland’s lab proposes that the library should encode numerous tumor antigens so the anti-tumor antibody profile can be used to accurately detect the presence of breast cancer on an individual basis. The lab will use the encoded 100-most abundant library genes to choose the most promising tumor antigen candidates for autoantibody screening. Dr. Egland and her team have established a robust method to produce native antigens that are recognizable by human antibodies. This method is suitable for secreted and membrane proteins and allows the antigens to form higher-order structures necessary for the efficient detection by the antibodies. These native antigens will be generated and screened with patients’ serum as the diagnostic assay.
Detection of a panel of tumor antigens can provide early, specific and personalized diagnosis for breast cancer patients, which will significantly improve outcomes and long-term survival of patients. Early diagnosis is essential in the fight against breast cancer and increases the likelihood of a woman being cured.