Disclosed herein is a
system that addresses all of the current challenges described above by combining three existing technologies and an improved nuclear
RNA delivery system to generate a first-in-class cellular therapy that can secrete a
cancer specific
suicide gene for the treatment of several cancers. Also disclosed herein is a 'Trojan-Horse' like genetic construct aimed at
engineering a chemo-sensitive dominant clone for adaptive therapy in cancers, such as
leukemia. In some embodiments, cells, such as
cancer cells from a subject, are engineered with suicide genes to promote a bystander effect in neighboring
cancer cells once returned to the subject. In some embodiments, these cells are further engineered to be clonally dominant, e.g. by deleting or mutating tumor
suppressor genes in the cells, overexpressing oncogenes, or any combination thereof. Once the engineered cells have reached a target clonal dominance, the
suicide gene can be induced, thereby promoting the bystander effect.