In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination

Chao Wang1,2, Jinqiang Wang1,2, Xudong Zhang1,2

  • 1Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA.

Insights

This study introduces a novel scaffold delivering gemcitabine and anti-PD-L1 therapy directly to tumors. This approach enhances anti-tumor immunity and promotes tumor regression, preventing recurrence in preclinical models.

Area of Science:

  • Biomedical Engineering
  • Immunotherapy
  • Drug Delivery Systems

Background:

  • Low-immunogenic tumors exhibit poor response to immune checkpoint blockade (ICB) therapies targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway.
  • Immune checkpoint blockade (ICB) therapy can lead to significant side effects in responding patients.

Purpose of the Study:

  • To engineer a localized therapeutic delivery system combining chemotherapy and immunotherapy for enhanced anti-tumor immune response.
  • To develop a novel scaffold for in situ formation and programmed release of gemcitabine (GEM) and an anti-PD-L1 antibody (aPDL1).

Main Methods:

  • Fabrication of a reactive oxygen species (ROS)-degradable hydrogel scaffold for controlled drug release within the tumor microenvironment (TME).
  • In situ administration of the scaffold to release GEM and aPDL1 with distinct release kinetics.
  • Evaluation of the scaffold's efficacy in promoting immunogenic tumor phenotype and immune-mediated tumor regression in tumor-bearing mice.

Main Results:

  • The engineered aPDL1-GEM scaffold successfully elicited an immunogenic tumor phenotype in vivo.
  • The scaffold demonstrated significant immune-mediated tumor regression in preclinical models.
  • Treatment with the aPDL1-GEM scaffold prevented tumor recurrence after primary tumor resection.

Conclusions:

  • The developed ROS-degradable hydrogel scaffold offers a promising strategy for localized delivery of combination therapy (GEM and aPDL1).
  • This localized approach enhances anti-tumor immunity and achieves durable tumor regression, highlighting its potential for treating low-immunogenic tumors and preventing recurrence.

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.2K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.9K
What is a Species?01:17

What is a Species?

Overview
50.6K
Formation of Species01:31

Formation of Species

Speciation describes the formation of one or more new species from one or sometimes multiple original species. The resulting species are discrete from the parent species, and barriers to reproduction will typically exist. There are two primary mechanisms, speciation with and without geographic isolation—allopatric and sympatric speciation, respectively.
45.5K
Keystone Species01:39

Keystone Species

Measures of species biodiversity, such as richness (i.e., the number of species present) and evenness (i.e., their relative abundance), describe an ecological community’s structure. Many factors affect community structure, including abiotic factors (e.g., sunlight and nutrients), disturbances (e.g., fire or flood), species interactions (e.g., predation or competition), and chance events (e.g., foreign species invasion). Certain species—such as keystone species—also play a...
25.0K
Treatment for Pulmonary Arterial Hypertension: Oxygen Therapy for Respiratory Failure01:16

Treatment for Pulmonary Arterial Hypertension: Oxygen Therapy for Respiratory Failure

Oxygen therapy has emerged as a significant tool in enhancing the quality of life for patients suffering from pulmonary arterial hypertension (PAH). While this therapy has principally been studied on patients with significant hypoxemia, this therapeutic approach helps prevent potential organ damage and can be administered in the comfort of one's home.
Oxygen therapy is vital in increasing and maintaining blood oxygen levels in PAH patients. As a result, it aids in reducing fatigue,...
636