A new mRNA-based cancer vaccine shows potential in eliminating tumours and preventing recurrence in mice.
Cancer vaccines are a controversial topic with plenty of research dating back years in this area, however, there has been minimal success. An innovation from Tufts School of Engineering could change this narrative. They have found a method of targeting cancer in mice with a vaccine that is so strong and precise, that it eliminates tumours and prevents their recurrence.
The cancer vaccine works similarly to COVID-19 vaccines from Pfizer and Moderna. They deliver mRNA in tiny lipid bubbles fusing with cells in the body, allowing the cells to “read” mRNA and produce viral antigens, which activate the immune system. The cancer vaccine also delivers mRNA in tiny bubbles, but it codes for antigens in cancer cells, and the bubbles are called lipid nanoparticles to focus on the lymphatic system, so the response is more potent.
“What we are doing now is developing the next generation of mRNA vaccines using lipid nanoparticle delivery technology, with the ability to target specific organs and tissues,” said Qiaobing Xu, a professor of biomedical engineering. “Targeting the lymphatic system helped us to overcome many of the challenges that have faced others in developing a cancer vaccine.”
The research was reported in the Proceedings of the National Academy of Sciences.
Developing an mRNA cancer vaccine
Over 20 mRNA have been tested in clinical trials, but a large proportion of the mRNA ends up in the liver, increasing the risk of liver inflammation and damage. Cancer vaccines would be more effective and long-lasting if more of the mRNA is directed to the lymphatic system, where B cells, T cells, and other immune system cells are concentrated and can fight cancer cells.
The current lipid nanoparticles (LNPs) found in the Pfizer COVID-19 vaccine favoured delivery to the liver, as opposed to the lymphatic system, by a four-to-one ratio. The researchers reversed that selectivity with their novel LNP to choose the lymphatic system over the liver by a three-to-one ratio. The lymphatic system plays an important role and is a crucial target for vaccines because this is where immunity against a cancer antigen is acquired.
Training dendritic cells and macrophages
A key element of a cancer vaccine is the participation of dendritic cells and macrophages; they work in the immune system to introduce the antigens to the T and B cells and fire them up.
With more vaccines going to the lymph nodes, the researchers revealed that the cancer vaccine was absorbed by around a third of dendritic cells and macrophages. This is significantly more than the capabilities of conventional vaccines, and more dendritic cells and macrophages mean more trained B and T cells and a more potent response against tumours carrying the same antigen found in the vaccine.
When treating the mice with metastatic melanoma, the lymph-targeted vaccine showed significant inhabitation of tumours and a 40% rate of complete response of no tumours with no recurrence in the long-term when it was combined with another existing therapy which prevents cancer cells from suppressing an immune response.
All the mice ended up in remission, and no new tumours formed when injected later with metastatic tumour cells, showing that the cancer vaccine led to excellent immune memory.
“Cancer vaccines have always been a challenge because tumour antigens don’t always look so ‘foreign’ like antigens on viruses and bacteria, and the tumours can actively inhibit the immune response,” said Jinjin Chen, a postdoctoral research fellow at Tufts University who is part of the Qiaobing Xu’s research team. “This cancer vaccine evokes a much stronger response and is capable of carrying mRNA for both large and small antigens. We are hoping that it could become a universal platform not only for cancer vaccines but also for more effective vaccines against viruses and other pathogens.”
