The problem with current immunotherapies is that they can trigger a wide range of auto-immune side effects: skin, lungs, gastrointestinal, thyroid, pituitary, l

The problem with current immunotherapies is that they can trigger a wide range of auto-immune side effects: skin, lungs, gastrointestinal, thyroid, pituitary, liver, and more. Each dose is like spinning a roulette wheel and hoping it lands on "cancer cell" instead of a useful organ. These side effects can often be dampened with high dose steroids, but they can persist for a very long time. After all, that's why immunotherapy is so exciting, it creates a durable response via immune memory. In my opinion the next big step will be injecting drugs like ipilimumab (Yervoy) plus adjuvants directly into solid tumours and malignant fluids. This would lower the total dose, reducing the chance of systemic side effects, while still delivering a high concentration where it is needed most: where dendritic cells carrying tumour antigens meet T cells in the nearest lymph node. The subsequent immune response will still provide a systemic benefit. For example, a recent melanoma study saw an abscopal (distant) response in 10 out of 12 patients with intra-tumoral treatment with ipilimumab + IL-2, with no serious distant side effects [1]. (Yes this is a very small study, but bear in mind response rates to systemic ipilimumab are normally more like 15%.) Unfortunately I wouldn't expect a company like Bristol-Myers Squibb to fund these kind of studies. The current model for pricing is by the mg, and intra-tumoral treatments use about 100 times less product than systemic treatments. Other drugs like nivolumab/pembrolizumab would still need to be delivered systemically because they operate on the front-line where T cells meet cancer cells. The step after intra-tumoral treatment will be generating and amplifying the immune response in a test tube instead of in the body. This is also very promising. [2] [1] http://www.ncbi.nlm.nih.gov/pubmed/27391442 http://www.ncbi.nlm.nih.gov/pubmed/27391442 [2] http://www.ncbi.nlm.nih.gov/pubmed/26894495 http://www.ncbi.nlm.nih.gov/pubmed/26894495