2 research outputs found

    Biomaterial techniques to evaluate and engineer the tumor immune microenvironment in breast cancer and melanoma

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    Immunotherapy has emerged as the most promising new approach to increase cancer patient survival through its potential to treat both advanced disseminated disease and protect against recurrence. However, response rates in advanced melanoma and the most aggressive and deadliest type of breast cancer, triple-negative breast cancer (TNBC) are disappointingly low: only 20-40% and ~16% of patients, respectively, respond to immune checkpoint blockade (ICB) therapy. Despite immunotherapy’s potential in boosting anti-tumor immune response, tumor-induced immune suppression subverts both its development and effects. Overcoming tumor immune suppression, the mechanisms of which are still poorly understood, is thus a critical hurdle to improving the efficacy of immunotherapy in reducing the mortality associated with advanced melanoma and TNBC. Through this research, sophisticated immunological characterization approaches and engineered biomaterial techniques have been applied to preclinical tumor models to analyze and engineer the in vivo melanoma and breast tumor immune microenvironment. The central hypothesis of this work is that modeling immune suppression underlying melanoma and TNBC disease progression will reveal mechanisms of immunotherapeutic resistance to inform the development of improved immunotherapeutic strategies. The goal of this work is to utilize bioengineering approaches and techniques to manipulate and analyze immune suppressive mechanisms within the tumor microenvironment (TME) that result in disease progression. This has resulted in the following outcomes: 1) improved understanding of the tumor immune microenvironment throughout the development and progression of melanoma and TNBC; 2) novel models with which to analyze antigen (Ag) sensing and model the breast TME; and 3) insight into optimal immunotherapeutic strategies for both melanoma and TNBC.Ph.D

    Elicitation of stem-like CD8+ T cell responses via lymph node-targeted chemoimmunotherapy evokes systemic tumor control

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    Background Tumor-draining lymph nodes (TdLNs) are critical in the regulation of local and systemic antitumor T cell immunity and are implicated in coordinating responses to immunomodulatory therapies.Methods Biomaterial nanoparticles that deliver chemotherapeutic drug paclitaxel to TdLNs were leveraged to explore its effects in combination and immune checkpoint blockade (ICB) antibody immunotherapy to determine the benefit of TdLN-directed chemoimmunotherapy on tumor control.Results Accumulation of immunotherapeutic drugs in combination within TdLNs synergistically enhanced systemic T cell responses that led to improved control of local and disseminated disease and enhanced survival in multiple murine breast tumor models.Conclusions These findings suggest a previously underappreciated role of secondary lymphoid tissues in mediating effects of chemoimmunotherapy and demonstrate the potential for nanotechnology to unleashing drug synergies via lymph node targeted delivery to elicit improved response of breast and other cancers
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