Interleukin-2, a cytokine that helps the immune system fight disease, is an FDA-approved treatment, but it has been associated with selectivity, toxicity and dosing issues. Those shortcomings have inspired a wave of biotechs trying to create the next generation of IL-2 therapies.
Now, Rice University researchers say they did so using beadlike implants.
In a mouse study, the researchers used the implants to deliver cells engineered to produce the natural compound, surrounded by a protective shell. The therapy helped eliminate tumors in 100% of the mice with ovarian cancer and in seven of the eight mice with colorectal cancer, the researchers said in the journal Science Advances this month.
Omid Veiseh, Ph.D., leader of the Rice lab and study co-author, is co-founder of Avenge Bio. The nascent Massachusetts startup, flush with a $45 million series A revealed in January, will take the drug technology into the clinic in the second half of this year, the biotech said in a statement about the study. Avenge has a license for the tech.
The cancers were eradicated within six days in some of the mice, the researchers said. The treatment was administered just once, but a second course could be administered safely if necessary, they said.
The treatment also sparked a stronger immune response than other IL-2 treatments because the implants delivered higher concentrations of the compound specifically to the tumors rather than to off-target areas, the researchers said. An IV formulation would be "extremely toxic," study co-author Amanda Nash said in a statement.
Cancers of the pancreas, liver, lungs and other organs could be targeted by the tech, the researchers said. A different cytokine could be used, too, by loading the beads with engineered cells that produce the desired compound, the researchers said.
To protect the beads' cytokine factories from immune attacks, the researchers created a shell using materials the immune system screens as foreign objects but not as threats to be addressed immediately.
“We found foreign body reactions safely and robustly turned off the flow of cytokine from the capsules within 30 days," Veiseh said in a statement.
IL-2 has been on the market since the early 1990s, when Proleukin was initially approved to treat renal cell carcinoma, and it has since racked up other regulatory nods for melanoma and other cancers.
Venture capital groups and Big Pharmas alike have been doling out money and inking deals in recent years to bankroll a new wave of IL-2 biotechs that want to quash the side effects and limitations of the original treatments.
Merck shelled out $1.9 billion in February 2021 to acquire Pandion Therapeutics, and Pfizer joined Novartis in backing Anaveon to bankroll the biotech's IL-2 agonist in solid tumors in December 2021.