For newborn and elder patients, it is often difficult to obtain enough T cells with good quality to generate patient-specific CAR-T cells. To make CAR-T therapy more accessible, it is highly desirable to develop an allogeneic adoptive transfer strategy, in which universal CAR-T cells derived from T cells from healthy donors can be applied to treat multiple patients. For this strategy to work, the αβ T-cell receptor (TCR) on allogeneic CAR-T cells needs to be eliminated to avoid graft-versus-host-disease (GVHD), and human leukocyte antigens class I (HLA-Is) on CAR-T cells need to be removed to minimize their immunogenicity.
Significant efforts have been made to use gene-editing technologies to develop next-generation adoptive T cell therapies. Indeed, the application of gene editing to immunotherapy can potentially allow for finer tuning of the immune response, permitting more specific activity, enhanced immune cell function, and the potential for “off-the-shelf” use.