Delivery Systems Developed for Treatment Combinations to Improve Adoptive Cell Therapy

Abstract Adoptive cell therapy (ACT) has shown great success in the clinic for treating hematologic malignancies. However, solid tumor treatment with ACT monotherapy is still challenging, owing to insufficient expansion and rapid exhaustion of adoptive cells, tumor antigen downregulation/loss, and dense tumor extracellular matrix. Delivery strategies for combination cell therapy have great potential to overcome these hurdles. The delivery of vaccines, immune checkpoint inhibitors, cytokines, chemotherapeutics, and photothermal reagents in combination with adoptive cells, have been shown to improve the expansion/activation, decrease exhaustion, and promote the penetration of adoptive cells in solid tumors. Moreover, the delivery of nucleic acids to engineer immune cells directly in vivo holds promise to overcome many of the hurdles associated with the complex ex vivo cell engineering strategies. Here, these research advance, as well as the opportunities and challenges for integrating delivery technologies into cell therapy s are discussed, and the outlook for these emerging areas are criticlly analyzed.