25 October 2021
Getting smart about cancer immunotherapy
Published online 28 January 2021
A smart hybrid material forms the foundation of a delivery system for personalized and targeted cancer immunotherapy.
A drug-loaded smart hybrid material has shown promise in blocking immune-evading cancer proteins, restoring T cell activity so they can attack and halt the growth of cancer cells.
Scientists in Saudi Arabia, the United Arab Emirates, and China loaded the cancer immunotherapy drug, Nivolumab, on to a metal organic framework called ZIF-8, made of zinc ions bound to methylimidazole ligands. The delivery system was used to stop the proliferation of leukaemia and breast cancer cells in petri dishes and in mice. The system was also able to selectively target and shrink breast cancer in mice by coating the system with breast cancer cell membrane.
“Such a coated hybrid material could reduce off-target delivery and immune-related side effects, improving the sensitivity of tumours to the drug,” says supramolecular chemist, Niveen M. Khashab, from King Abdullah University of Science and Technology, Saudi Arabia.
The biocompatible material is a step towards personalized immunotherapy for cancers, she says.
Some tumours evade the immune system by expressing proteins that inhibit the activity of T cells: immune cells that fight against pathogens and tumours. Nivolumab is an antibody that blocks these proteins so that T cells can actively attack the cancer cells.
The new delivery system releases small doses of Nivolumab when it reaches the slightly acidic microenvironment of tumours. This slow release is expected to reduce drug-related toxicity.
Coating the system with the cell membrane of a specific breast cancer led to its accumulation inside that tumour within three hours, even in the presence of other types of tumour cells, eventually showing more than 70 per cent cancer inhibition efficiency.
Breast-tumour-bearing mice treated with the coated material lived longer than mice treated with free Nivolumab, Nivolumab coated with cancer cell membrane, and uncoated Nivolumab-loaded ZIF-8.
The team plans to probe and modulate the material further to scale up its production for therapeutic purposes.
Alsaiari, S. K. et al. Sustained and targeted delivery of checkpoint inhibitors by metal-organic frameworks for cancer immunotherapy. Sci. Adv. 7, eabe7174 (2021).