Cell-based cancer immunotherapy has revolutionized the treatment of hematological malignancies. Specifically, autologous chimeric antigen receptor-engineered T (CAR-T) cell therapies have received approvals for treating leukemias, lymphomas, and multiple myeloma following unprecedented clinical response rates. A critical barrier to the widespread usage of current CAR-T cell products is their autologous nature, which renders these cellular products patient-selective, costly, and challenging to manufacture. Allogeneic cell products can be scalable and readily administrable but face critical concerns of graft-versus-host disease (GvHD), a life-threatening adverse event in which therapeutic cells attack host tissues, and allorejection, in which host immune cells eliminate therapeutic cells, thereby limiting their antitumor efficacy. In this review, we discuss recent advances in developing stem cell-engineered allogeneic cell therapies that aim to overcome the limitations of current autologous and allogeneic cell therapies, with a special focus on stem cell-engineered conventional αβ T cells, unconventional T (iNKT, MAIT, and γδ T) cells, and natural killer (NK) cells.
Keywords: T cell receptor (TCR); allogeneic cancer therapy; chimeric antigen receptor (CAR); graft-versus-host disease (GvHD); off-the-shelf cell therapy; stem cell engineering.