Integrating Low-Cost Paper-Based Devices and Personalized Immunotherapeutics to Treat Triple Negative Breast Cancer

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Integrating Low-Cost Paper-Based Devices and Personalized Immunotherapeutics to Treat Triple Negative Breast Cancer Summary After a breast cancer patient has an initial appointment with her clinician, one possible outcome is that the cancer tests positive for one or more clinically significant cell surface “biomarkers”, most notably estrogen receptor (ER), progesterone receptor (PR), or HER2. In this relatively good scenario, the patient would likely be prescribed a personalized therapy such as a hormone therapy (in the case of ER+ and/or PR+ cancers) or with drugs that specifically target HER2+ cells (e.g. the monoclonal antibody, mAb, Herceptin™). These personalized drugs are less toxic than general anti- cancer drugs such as chemotherapeutic cocktails. In a different, and relatively dire scenario, a patient is told she has “triple negative” breast cancer (ER-, PR-, HER2-), meaning her cancer cells lack hormone receptors like ER or PR, and lack HER2. Triple negative breast cancer (TNBC) represents 15-20% of all breast cancer cases, and disproportionately affects minority populations. Without personalized therapies, this patient is now left to suffer through treatment with non-targeted and toxic drugs (chemotherapeutics) that come with a host of debilitating side effects. Commonly, drastic measures, such as mastectomy, are required in order to fully remove all tissue that could serve as a source of, or substrate for, new tumors. The five-year survival outcomes of populations that test positive for HR and/or HER2, and TNBC patients substantially differs as well. For patients who test positive for HR and/or HER2 with regional breast cancer, five-year survival is ~82-89%, but 65% for TNBC. Clearly, new technologies and approaches are required to target TNBC and provide these patients the same therapeutic opportunities that patients that test positive for HR or HER2 biomarkers have. Here, we propose a fundamentally different approach to personalized medicine, which will dramatically change how we treat TNBC, particularly in lower income minority populations. We will evolve small proteins to selectively bind a patient’s breast cancer cells, irrespective of the specific changes to the cell surface that have occurred as a result of breast cancer. These proteins will be fused to other proteins that provide stability in the body, and recruit antibodies from the patient’s serum to TNBC cells, resulting in their targeted destruction. We will pair our TNBC-targeting immunotherapies (drugs that use the immune system to destroy TNBC cells) with a low-cost paper-based platform, which will allow simple, accessible, and routine assessment of our TNBC-targeting proteins, and allow clinicians to select which members should make up a combination therapy. The diagnostic platform will also allow clinicians to monitor the effectiveness of each member of the cocktail over the course of treatment (as cancer cells mutate), and select alternative members and/or replacements when necessary. Collectively, this work represents necessary and exciting advances in the integration of low-cost approaches to TNBC-targeting, and personalized, drug discovery, and the optimization and monitoring of these immunotherapeutic cocktails over the course of treatment.