Immune surveillance

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.

Immunotherapy is often given for two years or until it stops working, but responses can last long after stopping. Trials that randomly assign responders to stop or continue would show whether the extra year is needed.

Small triple-negative tumours packed with immune cells almost never come back. The idea is to skip chemotherapy for those patients.

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.

Stomach cancer now has three add-on biomarkers (HER2, PD-L1, Claudin 18.2) that often overlap. Test whether combining two add-ons beats picking one.

Add immunotherapy to the two targeted pills in the most aggressive thyroid cancer, because the combination has produced multi-year survivors in early series.

Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.

A single-centre trial at Tata Memorial found that adding nivolumab at about a twentieth of the usual dose to chemotherapy improved outcomes in head and neck cancer. Confirmatory trials against standard-dose immunotherapy are needed before low-dose labels could make immunotherapy affordable for millions.

Immunotherapy antibodies stay active in the body for weeks, yet are often given every two or three weeks. After a few months, spacing doses out to every two or three months might work as well, with fewer hospital visits and much lower cost.