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Immunoengineering Seminar Series

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Maggie Manspeaker
Graduate Student, Thomas Lab

"Elicitation of Stem-like CD8+ T Cell Responses via Lymph Node-targeted Chemoimmunotherapy Evokes Systemic Tumor Control"


Tumor-draining lymph nodes (TdLNs) are critical in the regulation of local and systemic anti-tumor T cell immunity and are implicated in coordinating responses to immunomodulatory therapies. Herein, 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. 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. 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 LN targeted delivery to elicit improved response of breast and other cancers.


Fredrick Bulondo
Graduate Student, Babensee Lab

"Optimization of IL-10 Incorporation for Dendritic cells Encapsulated in PEG-4MAL Hydrogel"


Biomaterials and immunoengineering research has enabled the development of advanced therapies to treat cancer, autoimmunity, and other immune-related pathologies. While much effort has been contributed to biomaterials for immunostimulatory applications such as vaccines and cancer, there has been far less focus on biomaterials that promote tolerance and regulatory mechanisms. Here, we seek to develop a biomaterial construct system for delivery of Dendritic cells (DCs) as therapies against Multiple Sclerosis, an autoimmune inflammatory disease that causes demyelination of the neurons in the Central Nervous System (CNS).

This biomaterial system is comprised of a poly(ethylene glycol)- 4 arm maleimide (PEG-4MAL) hydrogels conjugated with the immunosuppressive cytokine, interleukin, IL-10, which is injectable, in situ crosslinkable and degradable system for localized delivery of immunosuppressive DCs. Henceforth, it important to incorporate IL-10 with hydrogels encapsulating DCs because this immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype which consequently enhances cell viability and optimizing the system’s  immune modulatory functionality. The amount of IL-10 incorporated in hydrogel is expected to maintain incorporated DC viability, immunosuppressive phenotype and protection against pro-inflammatory insult as compared to hydrogel-incorporated DCs without IL-10. Furthermore, released IL-10 from implanted hydrogels is expected to promote DC phenotypic stability and mute the in vivo inflammatory response due to the foreign body response or the autoimmune environment. 
Based on preliminary results previously conducted in the laboratory, hydrogels loaded with 50 ng of IL-10 exhibited an effect on DC viability, phenotype and resistance to pro-inflammatory stimulus compared to DCs incorporated in hydrogels without IL-10.  The benefit of IL-10 presence in the hydrogel was apparent as far as attenuating the increase in CD86 expression upon addition of a maturation stimulus but the effect was moderate.
In the current studies, we seek to optimize this system by identifying the optimal initial loading amount of IL-10 to incorporate in the hydrogel and controlling the degradability of the hydrogel to control the release rate of IL-10 from the gel. Therefore, I anticipate identifying the amount of IL-10 and the release rate profile that is optimal for immunosuppressive viability and functionality for incorporated DCs for expected in vitro and in vivo function.

Upcoming Seminars: 

** This is the last seminar for Spring 2022. Seminars will resume in the fall. If you are interested in being a speaker please reach out to the organizers. 
 

Status

  • Workflow Status: Published
  • Created By: Colly Mitchell
  • Created: 04/11/2022
  • Modified By: Colly Mitchell
  • Modified: 04/18/2022

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