Experimental Hydrogel Delivers Targeted Chemotherapy, Immunotherapy

A novel injectable gel scaffold was able to deliver a combination of chemotherapy and immunotherapy to tumors in a sequential fashion, according to a study published by Science Translational Medicine.
 
These results in animal models suggest that the targeted approach may help increase the therapeutic benefits for patients with tumors or after surgery, according to the authors.
 
Thus far, the new approach showed efficacy in 2 types of melanoma and breast cancer, but the authors hypothesize it could be used in other types of tissue.
 
Importantly, the findings showed that local delivery of the combination treatment prevented disease recurrence after surgery.
 
“We’ve created a simple method to use chemotherapy while leveraging the biology of the tumor and our natural defense against foreign invaders to beat back tumor development with limited side effects,” said senior author Zhen Gu, PhD. “We have a lot more work to do before human clinical trials, but we think this approach holds great promise.”
 
A hurdle many immunotherapies face is that many cancers lack the characteristics needed for the treatment to recognize and attack tumors cells, which are called low-immunogenic tumors, according to the study.
 
Oncologists have tried to treat these tumors by administering chemotherapy first followed by immunotherapy; however, this method is not always successful for low-immunogenic tumors.
 
To address this need, the researchers developed a bioresponsive scaffold system, which is a hydrogel that can contain therapeutic particles.
 
“The trick is that the gel can be formed quickly inside the body once a biocompatible polymer and its crosslinker are mixed together,” said co-lead author, Jinqiang Wang, PhD. “We made sure that one of these agents can be cleaved apart by reactive oxygen species, or ROS—a natural chemical byproduct of cell metabolism.”
 
High levels of ROS are known to drive tumor development and growth, according to the study.
 
Once the hydrogel was developed, it was then loaded with gemcitabine chemotherapy and an anti-PD-L1 inhibiting immunotherapy.
 
When injected into the tumor, the hydrogel amplifies the characteristics that are identifiable by immunotherapies, according to the study. Then, the scaffold breaks down and releases gemcitabine, followed by immunotherapy.
 
“The cytotoxic chemotherapy can first kill some cancer cells and enhance the sensitivity of the tumor toward ICB therapy, which then stimulates the effectiveness of the ICB therapy,” said co-author Gianpietro Dotti, MD. “With degradation of the gel, the ROS level in the tumor site can be reduced, which also helps inhibit tumor growth.”
 
This strategy was tested in B16F10 melanoma and 4T1 breast cancer. The authors noted that the breast cancer was low immunogenic.
 
When administered to these tumors, the hydrogel successfully made the microenvironment susceptible to treatment and reduced tumor size, according to the study.
 
The hydrogel was also tested at the surgical site following primary tumor removal and discovered a significant prevention of recurrence, according to the study.
 
“Regarding the potential of this approach, scientists should further investigate the biocompatibility of using the gel scaffold for clinical benefit,” Dr Gu said. “Meanwhile, we will optimize the dosages of combination drugs as well as treatment frequencies.”


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