The Chimeric antigen receptors (CARs) is located on T-cells. The CARs consist of a tumor cell recognition site and an intracellular T-cell activation site. After the tumor cell recognition site docks with a cancer cell, the activation site stimulates T-cell proliferation. Thus the T-cells attack cancer cells and eliminates them. The most elegant part of this new method is that the patients’ own T-cells are isolated from the blood of the patient and used for terminating the cancer cells. The T-cells are activated and genetically modified to produce CAR T-cells. The modified T-cells are then infused into the same patient. The procedure is expensive as the T-cells have to be modified for each patient individually.
CAR-T has not yet been demonstrated to be effective in solid tumors, which are much more common than blood cancers. But targets of solid malignancies are currently being tested in the clinic. So far in particular the more common solid cancers, such as those of the breast, colon and lung, have failed to respond significantly to CAR T-cell therapy attempts.
The greatest obstacle for the CAR T-cell therapy to overcome are severe side-effects. Most reported severe side-effects are linked to cytokine-release syndrome and neurological toxicity. Cytokine release syndrome has been observed following administration of antibodies. The cytokine release syndrome is potentially life-threatening. In 2016 Juno Therapeutics reported that during a clinical trial 5 of 68 patients who received JCAR015 died.
CD19‑targeted CAR T-cells have been investigated clinically for the treatment of B‑cell malignancies. The response rates were in the early clinical trials up to 94%. But some of the studies have only small numbers of patients or the observation time is very short. We still need confirmation that the remission rate will be enduring over longer periods and we need clinical trials with more patients to establish this new promising therapy further.