Outsmarting and outmuscling cancer cells with synthetic and systems immunology

Adoptive T-cell therapy has shown remarkable clinical efficacy in treating refractory hematological cancers. However, challenges presented by solid tumors impede the applicability of adoptive T-cell therapy to the majority of cancers. In order to engineer effective T-cell therapies targeting solid tumors, two synergistic design criteria-T-cell therapeutic programs and anti-tumor T-cell chassis-should be taken into consideration. Recent advances in synthetic biology have enabled genetic programming of therapeutic sense-and-respond modalities in T cells. Furthermore, systems-level integration of multi-omics datum have allowed researchers to holistically profile robust anti-tumor T-cell populations. In this review, we feature novel strategies that can be incorporated into adoptive T-cell therapy design-ushering in a new paradigm of solid tumor treatment options.