T cell engagers (TCEs) act as a bridge that one end binding to CD3 on T cells and the other end binding to a tumor-associated antigen (TAA) on tumour cells. TCEs physically bring cytotoxic T cells directly next to the tumour cells. This forced proximity triggers the T cells to activate, proliferate and destroy the cancer cells. TCEs redirect the immune responses to eliminate the tumour, independent of TAA presentation. The NCG-MHC-dKO mouse is developed by knocking out both murine MHC class I and class II molecules in NCG mice. GvHD in NCG-MHC-dKO mice is attenuated and the survival of huPBMC-NCG-MHC-dKO mice is significantly prolonged. The growth of NCI-H69 human small cell lung cancer and MM.1S human multiple myeloma were significantly delayed by Tarlatamab in huPBMC-NCG mice. These findings indicate that human immune system reconstituted NCG mouse is an ideal model for TCE efficacy evaluation.