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PhD Proposal by Paul Archer

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Paul Archer

BioE PhD Proposal Presentation

Date: Thursday, April 22, 2021

Time: 1:30 PM

BlueJeans Link: https://bluejeans.com/200664225

Meeting ID: 200 664 225

 

Advisor:  

Susan Thomas, PhD 

 

Committee Members: 

Julie Champion, PhD 

Brandon Dixon, PhD 

Valeria Milam, PhD 

Krishnendu Roy, PhD 

 

Transport mechanism and administration route influences on accumulation and targeted leukocyte access in the healthy and tumor draining LN 

Lymph nodes are tissues that mediate and organize the congregation of immune cells and are important in the priming of the adaptive immune response. This makes them targets of interest for a variety of immunomodulatory treatments, including cancer immunotherapy. However, achieving therapeutic access to the important leukocyte drug delivery targets within the lymph node can be difficult, as transport from the injection site to the lymph node and transport within the lymph node itself both present significant obstacles due to physical and cellular barriers. To aid in its function facilitating favorable and timely immune responses, the lymph node is a highly structured organ, which introduces compartmentalization of leukocyte subsets and size exclusion parameters to the movements of soluble materials within it; however the influences of these transport barriers on drug delivery system access to the cells involved in the adaptive immune response have yet to be systematically characterized. Furthermore, lymph nodes draining from melanoma tumors undergo significant structural remodeling that may influence drug delivery approaches most suitable for cancer immunotherapy targeted to the tumor-draining lymph node. The objectives of this proposal are to provide fundamental insight into the influences of transport mechanism, route of delivery, material properties, and cell-targeting effects on leukocyte access within the healthy and tumor-draining lymph node, which will be systematically tested using a panel of fluorescent tracers of varied size and flexibility, and nanoparticles with cell-targeted monoclonal antibody moieties in preclinical mouse models. It is hypothesized that delivery to lymph node resident leukocytes can be modulated through lymphatic vs blood vasculature routes of delivery, and that these influences will differ in the tumor draining lymph node due to vascularization changes and structural remodeling. Results will inform the development of improved immunomodulatory treatment delivery strategies broadly, and in the specific application of cancer immunotherapy.

Status

  • Workflow Status:Published
  • Created By:Tatianna Richardson
  • Created:04/09/2021
  • Modified By:Tatianna Richardson
  • Modified:04/09/2021

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