Researchers at Peking Union Medical College Hospital have mapped out why pairing two well-known cancer drugs can turn “sleepy” immune cells back into tumour killers.

In a new Perspective published today, they trace the story behind the newest lab-designed proteins: one end releases the brake called PD-1 on T cells, while the other end gently hands the same cells a safer, souped-up version of the growth signal interleukin-2 (IL-2).

Immune checkpoint inhibitors like programmed death-1 (PD-1) blockade have transformed cancer care, but their effectiveness as a standalone therapy is limited.

A key issue is that high PD-1 expression is linked to the terminal differentiation and exhaustion of immune cells, particularly T cells, creating a contradiction that reduces treatment efficacy and response rates.

​IL-2, a critical immune-regulating cytokine, was one of the earliest approved cancer immunotherapies.

However, its wide-ranging and complex effects have held back its full potential.

Recent research, as highlighted in the review, shows that combining PD-1 blockade with IL-2 can work synergistically.

This combination eases T cell exhaustion and boosts the cells' ability to fight tumours, leading to better treatment outcomes.

​Building on this discovery, scientists have developed bi-functional molecules.

These innovative substances can simultaneously block PD-1 and deliver IL-2 or its engineered variants directly to target immune cells.

The review catalogues all nine PD-1/IL-2 bi-functional agents now in clinical trials, mapping the field from IL-2Rbg -biassed/IL-2Ra-biassed designs to non-blocking PD-1 antibodies and the masked pro-drug design, details the mechanisms behind these bi-functional molecules, their potential in cancer treatment, and how they could drive future innovations in immunotherapy.

Found in the journal, Science Bulletin.

Source: Science China Press