An improved humanized mouse-human tumor model for immunogene therapy

摘要

Severe combined immunodeficient (SCID) mice lackfunctional B and T lymphocytes which make themamicable recipient for xenograft transplantation. Amplestudies have demonstrated uptake of human tumors andengrafment of human lymphocytes in the scid/scid mice.A human-lymphocyte-chimera-SCID mouse bearinghuman tumor is a model mimicking human cancer patientand can be valuable for studying immunogene therapeuticregimens on cancer. However, the existing NK functionand the leakiness of the scid/scid mouse strain greatlydiminish the engraftment rate of human tumors or humanimmune cells (usually around 60%). Here wedemonstrate using the scid/beige strain, which lacksfunctional B, T, and NK cells, significantly improvedrate of tumor uptake and human lymphocytereconstitution. A variety of unmodified or immuno-modulatory gene-transduced human tumor cells includingmelanoma, hepatoma, glioblastoma, and breast cancercells were successfully established in the scid/beige mice.Palpable tumors were usually conceived at 1 -