ReviewLife & Medical SciencesSynthetic immunity to break down the bottleneck of cancer immunotherapy

As a result of recent breakthroughs in cancer immunotherapies, unprecedented and durable remission, and even cure, has been reported in some patients. Importantly, this progress has been achieved, not by the induction of immunity, but by the delivery of immunity in the form of engineered antibodies (eAbs) or effector T cells. However, these single-target technologies have failed to result in a therapeutic effect in some patients, and evidence suggests that further advances depend on an effective strategy for coping with cancer heterogeneity and dynamics. A synthetic immunity (SI) strategy is proposed to achieve this goal. The fundamental basis of SI involves the generation of a panel of eAbs and antibody-retargeted CTLs designed to destroy all cell lineages of a cancer with high specificity. This goal can be achieved only when the composition of the eAbs is determined using a systematic approach, i.e., selecting the antigens targeted by the eAbs based on an epitope-tree illustrating the clonal antigen architecture of the cancer. Integration of technologies that increase the epitope breadth, eAb affinity and T cell activity will further enhance the efficacy of SI. Using DNA vectors to express the eAbs will be a safe, effective and affordable solution.