权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

整合低成本纸基设备和个性化免疫疗法来治疗三阴性乳腺癌

基本信息

批准号：
10556823
负责人：
Brian Richard McNaughton
金额：
$ 32.82万
依托单位：
DELAWARE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-20 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10556823
关键词：
Affect Affinity African American African American population Antibodies Antineoplastic Agents Appointment Binding Biological Markers Biological Products Breast Cancer Cell Breast Cancer Patient Breast Cancer cell line Cell Surface Proteins Cell Surface Receptors Cell surface Cells Childhood Clinic Combination immunotherapy Combined Modality Therapy Complex Delaware Development Devices Diagnostic Equipment Disease Drug Costs Drug usage Effectiveness Epidermal Growth Factor Receptor Escherichia coli Estrogen Receptors Excretory function Generations Goals High Risk Woman Hormone Receptor Human Immune Immune mediated destruction Immune system Immunotherapeutic agent Immunotherapy Incidence Left Localized Disease Low income Malignant Neoplasms Mammalian Cell Mastectomy Measures Methods Minority Groups Monitor Monoclonal Antibodies Mutate Operative Surgical Procedures Outcome Paper Patient Monitoring Patient-Focused Outcomes Patients Phage Display Pharmaceutical Preparations Population Production Progesterone Receptors Proteins Psyche structure Radiation Reporter Research Serum Signal Transduction Source Techniques Technology Tertiary Protein Structure Testing Therapeutic Tissues Trastuzumab Trauma Treatment Efficacy Treatment outcome Vaccination Woman Work aggressive breast cancer antibody-dependent cell cytotoxicity base cancer cell cancer health disparity cancer immunotherapeutics cancer immunotherapy cancer subtypes clinically significant cost design diagnostic platform drug discovery experimental study health equity hormone receptor-positive hormone therapy improved in vivo malignant breast neoplasm member nanobodies new technology novel strategies personalized approach personalized immunotherapy personalized medicine personalized therapeutic precision drugs receptor recruit side effect survival outcome targeted treatment triple-negative invasive breast carcinoma tumor virtual

项目摘要

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.

整合低成本的纸质设备和个性化