Antigen presentation

Individualised mRNA cancer vaccines take weeks to manufacture and work best against minimal residual disease. Making the vaccine at surgery and giving it only when a blood tumour DNA test turns positive matches both facts and concentrates the cost on the minority who will relapse.

Personal cancer vaccines target a list of mutations, some present in only part of the tumour, so the tumour can escape by losing them. Restricting vaccines and T-cell products to clonal mutations shared by every tumour cell, identified by multi-region sequencing, should close that escape route.

Some tumours change fast and escape drugs quickly; others are stable. A single validated score for how evolvable a tumour is would tell doctors how aggressively to combine treatments.

Resistance often arrives as the same few mutations. Teaching the immune system to recognise them in advance could remove the escaping cells while they are still rare.

People with Lynch syndrome have a very high lifetime cancer risk from a predictable set of mutations. Vaccinate them against those shared mutations before cancer appears.

Lynch syndrome tumours share predictable mutations the immune system can target. A vaccine in early trials could be tested to see if it prevents polyps and cancers in carriers.

Tumour mutational burden decides who gets immunotherapy in some settings, but every sequencing panel calculates it differently. A shared calibration would make the number mean the same thing everywhere.

Vaccines tailored to each patient's tumour mutations are showing real benefit but cost a fortune to make. Automate the whole process so a personalised vaccine costs about as much as a course of chemotherapy.

Cells chop up their internal proteins and display the pieces on their surface. That means even undruggable proteins inside the cell can be attacked from outside by the immune system.

Some tumours have broken the machinery that displays their identity to immune cells. Those patients cannot benefit from most immunotherapy and should be routed elsewhere.

Today's engineered T-cell therapies for sarcoma only work in the ~40-50% of people with one particular HLA type; new receptors for other HLA types would open them to everyone.

Today's T-cell-receptor drugs only work for people with one tissue type. Building versions for the other common types would roughly double who can be treated.

Vaccines can now encode dozens of a tumour's mutations, but only a minority provoke useful T cells. Learning the rules would make vaccines smaller, cheaper, and stronger.

Dozens of trials have collected immune, genomic and imaging data on the same drugs. Nobody can analyse them together, so the answer stays hidden in fragments.