- An injectable therapeutic gel can
hold chemo-immunotherapeutic drugs and deliver them to the tumor site.
- Upon reaching the tumor site, the
gel is degraded and first the chemotherapeutic agent is released followed
by the immunotherapeutic agent.
- The cytotoxic chemotherapeutic
first kills some cancer cells and enhances the sensitivity of the tumor
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
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
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.
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.
‘An injectable hydrogel can deliver both chemotherapeutics and immunotherapeutics to the tumor site in a sequential manner, attacking the cancer cells with two different therapeutic approaches.’
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."
"We have a lot more work to do before human clinical trials, but we
think this approach holds great promise," Gu concluded.
- 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
- Nano-hydrogels that attack cancer cells - (https://phys.org/news/2015-02-nano-hydrogels-cancer-cells.html#jCp)