Immune U-Turn

At the annual meeting of the American Association for the Advancement of Science in Washington, DC, Stan Riddell and colleagues reported on a trial with advanced leukemia patients. They infused the patients with their own, reprogrammed T-cells, engineered to express chimeric antigen receptors (CARs) that cause them to attack tumor cells. The results appear to be impressive. Of 29 patients with acute lymphoblastic leukemia, 27 showed no trace of cancer in their bone marrow following their infusions, while 19 of 30 non-Hodgkin lymphoma patients experienced partial or complete responses. Some of the patients had life expectancies of only a few months before joining the trial; more than two years on, they remain in remission.

It wasn’t entirely untrammeled good news; serious side effects caused by cytokine release syndrome (including fever, hypotension and neurotoxicity) were reported in 20 of the patients – and two died. A risk worth taking for patients with few other options, but a serious stumbling block for commercialization. The full study is set to be published in the next few months and time will tell if cancer researchers are able to rein in side effects while maintaining the stellar success rates of the therapy.

The study follows similar promising results in a number of small trials, making CAR T-cell therapy one of the hottest areas in cancer research. With the success of checkpoint inhibitors, cancer immunotherapy – once a fringe area – is well on its way to becoming a cornerstone of the anticancer arsenal. The origins of immunotherapy go back to the late 1800s, when New York doctor William Coley first administered his famous “Coley toxins” – based on killed bacteria – to cancer patients. Around 10 percent were cured, but unpredictable results led to skepticism, and the therapy was eventually sidelined by emerging radiotherapy and chemotherapy approaches.

A pattern of exciting discoveries in the lab followed by disappointing results in animal or human studies characterized the field for decades. The originator of the checkpoint inhibitor concept, Jim Allison, is quoted as saying that his mentors in the 1970s discouraged him from pursuing tumor immunotherapy, because it was seen as a discredited field. Up until the late-1990s, it looked as if immune mechanisms in cancer might never be clinically relevant, but the subsequent success of checkpoint inhibitors and renaissance of cancer immunotherapy should give hope to researchers in any field who have struggled to find translational success. Our intrepid pain researchers are certainly not ready to throw in the towel.

Charlotte Barker
Editor