New Injectable Gel Therapy To Deliver Both Chemotherapeutics And Immunotherapeutics

New injectable gel cancer therapy shows promise in attacking and treating cancer in a two-dimensional approach. When injected into the tumor, the therapy forms a gel to attack cancer cells. The gel contains both chemotherapeutics and immunotherapeutics which when delivered to the tumor site, are sequentially released to kill cancer. The gel-therapy scaffold was developed by a research team at UNC School of Medicine and NC State and is published in Science Translational Medicine. Chemotherapy is a conventional option of treatment for most types of cancers. However, other types of therapies including immunotherapy are also gaining momentum. While chemotherapy uses drugs to fight cancer, immunotherapy makes use of the body’s cells to attack the tumor within. The new study has developed a scaffold that holds both chemo and immunotherapeutic drugs and delivers them at the tumor site. The injectable gel scaffold containing combination therapy was found to significantly inhibit the recurrence of cancer after the primary tumor was surgically removed.

Cancer Immunotherapy

Mutations are spontaneous events that happen in every living cell. However, some mutations can lead to cancer. But our immune system is smart enough to recognize these mutations and destroy these cells. Unfortunately, sometimes cancer cells are lucky enough and manage to trick our immune system and evade immune attack by hijacking the immune system.

Immunotherapy tries to reset the hijacked immune system and thereby use it to kill cancer cells within. While it has great potential to treat cancers like melanoma, kidney cancer etc, it fails with low-immunogenic tumors, which lack the specific characteristics needed for the immunotherapy to recognize and attack the cancer cells. Attacking tumors with chemotherapy first has been found to increase immunotherapy efficacy.

How the gel therapy works

The scaffold is essentially a hydrogel, a material that is commonly used in contact lenses and diapers to control humidity. However, this study has given it a medical potential. The polymeric network can be loaded with therapeutics and injected into the tumor site.

"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, "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."

The hydrogel scaffold was loaded with a chemotherapeutic gemcitabine and an immunotherapeutic agent - anti-PD-L1 blocking antibody. When the gel reaches the tumor, the reactive oxygen species in the tumor degrade the gel releasing gemcitabine first, and then anti-PD-L1.

"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, PhD, professor of microbiology and immunology at the UNC School of Medicine. "With the degradation of the gel, the ROS level in the tumor site can be reduced, which also helps inhibit tumor growth."

This is what lead author Zhen Gu, PhD, associate professor in the joint UNC/NCSU Biomedical Engineering Department had to say about the potential therapy: "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."

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"We have a lot more work to do before human clinical trials, but we think this approach holds great promise," Gu concluded.

References:

1. Chao Wang, Jinqiang Wang et al. “In situ formed reactive oxygen species–responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy.” Science Translational Medicine, (2018) DOI: 10.1126/scitranslmed.aan3682
2. Nano-hydrogels that attack cancer cells - (https://phys.org/news/2015-02-nano-hydrogels-cancer-cells.html#jCp)

Source-Medindia