Last updated on November 2017

Identification of autoantibodies targeting genes implicated in metastatic cancer

Brief description of study

Identification of autoantibodies targeting genes implicated in metastatic cancer

Detailed Study Description

Cancer is the second-leading cause of death in the United States today. The majority of cancer deaths can be attributed to the metastatic spread of solid tumors to distant organs. Medical progress in the last century has aided in the earlier identification of cancers limited to the primary organ and subsequent cure of these cancers with a combination of modalities – surgery, chemotherapy, and/or radiation. However, once cancer has invaded organs outside its primary site, the prognosis is grim; cure rates for metastatic cancer are even worse. The treatments of metastatic colorectal and breast cancer have made great improvements in the last 30 years compared to most other malignancies; a subset of patients with metastatic disease can expect to live 5 years after diagnosis with treatments with the latest chemotherapy regimens, but there remains a considerable need for more targeted combination therapies with fewer side effects. An emerging field in the last decade has been cancer immunology – the contribution of the immune system in controlling the oncologic process. Within cancer immunology, the role of autoantibodies – antibodies that target host factors rather than a foreign invader (typically viruses or bacteria) - is relatively unexplored. It is unclear at this time whether autoantibodies in the setting of cancer are a marker of disease progression, disease containment, or both. Antibody-based drugs have become increasingly common therapeutic options for all types of diseases including myocardial infarction, asthma, and cancer. Most of the antibody therapeutics were developed in the lab using the hybridoma technology – a process which involves using mice to develop antibodies against the protein of interest and fusing the antibody-producing cell with a human cancer cell. A selection process then ensues to find the cell that produces the antibody with the highest binding affinity to the protein of interest; this process can be tedious and painstaking. A method to screen for antibodies of interest in humans and subsequently isolate the cell that produces that antibody has been pioneered at the Rockefeller University; this method avoids some of the limitations of the hybridoma technology. In previous work, our lab has identified novel proteins implicated in colorectal and breast cancer metastasis. Some patients with systemic lupus erythematosus (SLE) – an autoimmune disease – produce autoantibodies to proteins implicated in colorectal cancer metastasis to the liver. Some patients with colorectal and breast cancer produce autoantibodies to a protein involved in breast cancer metastasis to the lung. In this project we seek to screen subjects with colorectal cancer, breast cancer, and SLE for autoantibodies toward our proteins of interests. The identification of autoantibodies that hinder metastatic growth has tremendous prognostic and therapeutic implications.

Clinical Study Identifier: TX2318

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