Patient-Specific B-Cell Antibody Factories to Treat Metastatic Disease
Annual rept. 1 Aug 2012-31 Jul 2013
CONNECTICUT UNIV HEALTH CENTER FARMINGTON
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We propose to develop a panel of full length human anti-cancer antibodies derived from sentinel lymph nodes of individual patients. The application of sentinel lymph node mapping techniques as standard of care for cancer staging provides a unique resource to perform these studies. Our preliminary studies demonstrate that reactive B-cells can be selected from sentinel lymph nodes, cultured in the laboratory, and more importantly, induced to express human antibodies using tumor-derived extracts and activating cytokines. Immortalization of these selected clones using Epstein-Barr viral transformation provides a method to maintain these antibody producing cell lines as a renewable source of anti-cancer antibodies. Cancer-specific abnormal proteins are likely to arise from genetic mutation, excess protein expression, or the presence of non-self epitopes resulting from aberrant posttranslational modification. The immune system is designed to trigger local immune responses to abnormal epitopes and develop protective antibodies against what are recognized as foreign molecules. We expect that some of these antibodies may be specific to unique mutations or proteins found in individual patients whereas others may target abnormal proteins arising from processing errors which are likely to be present in many breast cancers. The development of a panel of antibodies from multiple patients will provide both diagnostic and therapeutic applications to the majority of breast cancer patients.
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