Peptide droplets cut colorectal tumor growth about 67% in mice

At Nanyang Technological University in Singapore, Professor Ali Miserez and Ph.D. student Chen Zilin hold a test tube containing microscopic peptide droplets. In small-animal experiments, the patent-pending system reduced the growth of colorectal tumors by about 67% in mice.

The droplets target a molecular brake used by tumors to evade immune attack. PD-1 sits on the surface of T cells, immune cells that can recognize and kill abnormal cells, while PD-L1 is displayed by tumor cells. When the two proteins bind, they send the T cell a stop signal. The NTU approach uses small interfering RNA, or siRNA, to destroy the messenger RNA instructions that tell cells to make PD-1 or PD-L1.

The delivery system uses two separate formulations. siPD-1@THC carries siRNA against PD-1 and has anti-CD3 antibodies on its surface to help it enter T cells. siPD-L1@HC carries siRNA against PD-L1 into colorectal cancer cells. Laboratory experiments found that the combination increased T-cell activation and immune signaling, helping T cells kill more colorectal cancer cells.

NTU chose a difficult test rather than a tumor model already known to respond well to immunotherapy. Microsatellite-stable, or MSS, tumors make up about 85% of colorectal cancers, yet immune checkpoint inhibitors have limited clinical benefit against them; one reason is that these tumors tend to contain relatively few cancer-killing T cells. In the mouse study, the combined treatment suppressed tumor growth to a level comparable with anti-PD-1 and anti-PD-L1 antibody treatment used as a benchmark.

For patients, the practical meaning is limited for now: the reported result is in mice, and Chen said the team hopes to reproduce it in larger studies next. For drug developers, the possible payoff is a cheaper way to deliver the same immune-targeting strategy. NTU researchers estimate that siRNA production could potentially cost five to 10 times less than producing monoclonal antibody treatments if the approach is successfully developed and scaled up.

That estimate is conditional, not a demonstrated manufacturing cost. Professor Javier Montenegro García of the University of Santiago de Compostela, commenting independently, said the peptide droplets could support sustained release at the tumor site, improve penetration through the tumor environment and simplify manufacturing. The study was led by Miserez and published in Biomaterials.