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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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A Spheroid Killing Assay by CAR T Cells
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Toroidal-spiral particles as a CAR-T cell delivery device for solid tumor immunotherapy.

Hui Tang1, Maryam Zaroudi2, Yuli Zhu2

  • 1Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|September 6, 2023
PubMed
Summary

Biodegradable toroidal-spiral particles (TSPs) act as in vivo incubators for chimeric antigen receptor (CAR) T-cells. Peritumoral delivery of CAR-T cells using TSPs demonstrated superior solid tumor treatment efficacy in preclinical models.

Keywords:
Adoptive cellular therapyBiodegradable particleImmunotherapyIn vivo cell incubatorProgrammable releaseSelf-assembly

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Area of Science:

  • Biomaterials Science
  • Immunotherapy
  • Oncology

Background:

  • Chimeric antigen receptor (CAR) T-cell therapy shows promise for hematologic malignancies but faces challenges in solid tumors, including poor trafficking, toxicity, and antigen escape.
  • Current delivery methods for CAR-T cells often result in insufficient tumor infiltration and localized efficacy.

Purpose of the Study:

  • To develop and evaluate a novel biodegradable polymeric toroidal-spiral particle (TSP) as an in vivo cell incubator and delivery system for CAR-T cells in solid tumors.
  • To assess the efficacy of TSPs for localized delivery and sustained release of mesothelin (MSLN)-specific CAR-T cells in preclinical solid tumor models.

Main Methods:

  • Fabrication of millimeter-sized TSPs using crosslinked gelatin methacrylamine (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) with tunable degradation rates.
  • Co-encapsulation of collagen and MSLN CAR-T cells within the TSP's void volume for sustained proliferation, activation, and migration.
  • Evaluation of TSP-mediated peritumoral delivery of MSLN CAR-T cells in preclinical mouse solid tumor models, comparing outcomes to systemic and intratumoral injections.

Main Results:

  • TSPs demonstrated tunable degradation rates and appropriate mechanical properties for sustained release of co-encapsulated compounds.
  • The TSPs successfully promoted CAR-T cell proliferation, activation, and migration within the tumor microenvironment.
  • Peritumoral delivery of MSLN CAR-T cells via TSPs achieved superior antitumor effects compared to systemic and intratumoral administration in mouse models.

Conclusions:

  • Biodegradable TSPs serve as effective in vivo reactors for CAR-T cell expansion and localized delivery.
  • TSP-mediated delivery offers a minimally invasive approach to enhance CAR-T cell efficacy against solid tumors while potentially reducing toxicity.
  • This innovative delivery system holds promise for improving CAR-T cell therapy outcomes in solid tumor treatment.