Cytokine delivery platform for eradication of intraperitoneal tumors

A new cancer therapy has completely destroyed advanced ovarian and bowel tumors in just six days.

Clinical trials are expected to begin in the next few months, after results on mice were described as “very exciting”.

Pinhead-sized drug ‘factories’ were delivered to give continuous, high bursts of a protein that boosts the immune system.

“We just administer once, but they keep making the dose every day, where it’s needed until the cancer is eliminated,” said a co-author.

“Once we determined the correct dose—how many factories we needed—we were able to eradicate tumors in 100% of animals with ovarian cancer and in seven of eight animals with colorectal cancer.”

The tiny beads have a protective shell containing cells engineered to produce interleukin-2. They could be used to fight the most lethal cancers, including those of the pancreas, liver and lungs.

They can be implanted with minimally invasive surgery, and could be tested on human patients by autumn, so they can get them into hospitals as quickly as possible.
For the mixture, the team chose only components that had previously proven safe for humans.

The drug-producing beads were placed next to tumors in lab rodents and within the lining of the abdominal cavity, a sack-like lining that supports the intestines, ovaries, and other abdominal organs, and limits exposure elsewhere.

“A major challenge in the field of immunotherapy is to increase tumor inflammation and anti-tumor immunity while avoiding systemic side effects of cytokines and other pro-inflammatory drugs,” said another coauthor.

“In this study, we demonstrated that the ‘drug factories’ allow regulatable local administration of interleukin-2 and the eradication of tumor in several mouse models, which is very exciting.”

Interleukin-2 is a cytokine, a protein the immune system uses to recognize and fight disease, which has been approved as a cancer treatment by the US Food and Drug Administration.

Lead author said the beads provoke the strongest immune response to date.“If you gave the same concentration of the protein through an IV pump, it would be extremely toxic.

With the drug factories, the concentration we see elsewhere in the body, away from the tumor site, is actually lower than what patients need to tolerate with IV treatments. The high concentration is only at the tumor site.

The lead author said it opens the door to the same general approach to treat cancers of the pancreas, liver, lungs and other organs.

If a different cytokine is needed to target a specific form of cancer, the beads can be loaded with any immuno-therapeutic compound.

The bead’s outer shell shields its cytokine-producing cells from immune attacks, as they are made of materials the immune system recognizes as foreign objects, but not as immediate threats.

The senior author said, “We found foreign body reactions safely and robustly turned off the flow of cytokine from the capsules within 30 days.

In the research published in the journal Science Advances, they also showed they could safely administer a second course of treatment should it become necessary in the clinic.

Colorectal cancer is one of the most common cancers, while ovarian is particularly lethal because it is usually only diagnosed in the late stages.