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Immunoengineering Trainee Seminar
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“Thermosensitive Hydrogel Sustaining the Release of Lymph-draining Oligonucleotide Adjuvant Polyplex Micelles Improves Systemic Cancer Immunotherapy” - Samuel Lucas, Ph.D. Student, Thomas Lab
Abstract:
Immune checkpoint blockade (ICB) immunotherapies are a powerful tool in the clinical management of cancer, but response rates to ICB remain limited and treatment-related toxicities can be significant. Therapeutic efficacy of ICB can be enhanced by delivering synergistic immunomodulators to tumor-draining lymph nodes (TdLNs). However, achieving sustained release of small molecule immunomodulators into the lymphatics and TdLNs remains challenging. To address this limitation, a sustained release system for delivering oligonucleotide adjuvant to lymph nodes was developed. CpG oligonucleotide was complexed with a redox-responsive cationic polymer and mixed with F127-g-Gelatin to generate a thermosensitive hydrogel that releases lymph-draining polyplex micelles in situ. This CpG/BPEI-SS-/F127-g-Gelatin (CpG-HG) system enhanced the quantity and duration of CpG delivery to TdLNs following locoregional administration compared to free drug and enabled targeted, potent, and prolonged immunomodulation within TdLNs from a single administration. This augmented, localized immune response synergized with systemic ICB treatment in both markedly amplifying the systemic circulating CD8+ T cell response and improving anti-tumor therapeutic efficacy while enabling ICB dose reduction. These results highlight the potential for this drug delivery system as an adjunct to existing clinical ICB protocols to improve patient outcomes.
"Developing Human Immune Organoids to Decode B Cell Response in Healthy Donors and Patients with Lymphoma"- Zhe "Monica" Zhong, Ph.D. Student, Singh Lab
Abstract:
Understanding human B cell differentiation is vital for developing effective vaccines and therapies, especially in immunocompromised patients such as those with B cell lymphoma. Current models based on secondary lymphoid tissues like tonsils have provided valuable insights but remain limited by tissue availability, intrinsic inflamed microenvironments, and the inability to mimic the complex human lymphoid microenvironment. To overcome these barriers, I have developed synthetic hydrogel-based immune organoids that recreate key features of lymphoid tissue, including biophysical cues, chemokine gradients, and stromal–immune cell interactions, enabling robust B cell maturation from both tonsillar and peripheral blood-derived sources (PBMCs). These organoids support germinal center formation and plasma cell differentiation under physiologically relevant conditions. Leveraging this platform, I perform transcriptomic profiling of B cells from healthy donors and lymphoma patients to dissect the molecular mechanisms governing B cell fate decisions. Additionally, by integrating organoids with microfluidic devices, I spatially regulate chemokine gradients to study B cell selection dynamics in a controlled manner. Together, this work establishes a versatile system for modeling human immune responses and B cell disorders, paving the way for the development of next-generation immunotherapies and personalized treatment strategies.
The Immunoengineering Training Seminar Series is supported by the Center for Immunoengineering at Georgia Tech.
Status
- Workflow Status:Published
- Created By:Christina Wessels
- Created:05/29/2025
- Modified By:Christina Wessels
- Modified:05/29/2025
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