An engineered three-dimensional gastric tumor culture model for evaluating the antitumor activity of immune cells in vitro

Monolayer tumor culture models have been used for evaluating the antitumor activity of immune cells in vitro. However, their value in this research is limited. We used human gastric cancer cells (BGC823) and collagen hydrogel as a matrix to establish an engineered three-dimensional (3-D) tumor culture model in vitro. Tumor cells grew in 3-D culture and formed spheroids in the collagen matrix. Evaluation of the antitumor activity of cytokine-induced killer (CIK) cells revealed that, compared with the 2-D cell culture models, CIK cells migrated towards the tumor cells and destroyed the spheroids and tumor cells in the engineered 3-D tumor culture model. The cytotoxicity of CIK cells against the tumor cells in the engineered 3-D tumor culture model was lower than that in 2-D tumor culture models at 12-36 h post-interaction, but there was no significant difference in the cytotoxicity at later time points. Further analysis indicated that dendritic cell-activated CIK cells had a significantly higher level of cytotoxicity against tumor cells, compared with CIK and anti-CEA/CD3-treated CIK cells, in the engineered 3-D tumor culture model. Our data suggest that the engineered 3-D gastric tumor culture model may better mimic the interaction of immune cells with tumor cells in vivo than the 2-D tumor culture models, and may be used for evaluating the antitumor activity of immune cells in vitro.