Figure 4.

OX40 costimulation reduced antitumor efficacy of chimeric antigen receptor (CAR)-redirected cytokine-induced killer (CIK) cells. (a) Rag^−/− common γ-chain^−/− mice were engrafted subcutaneously with CEA⁺ C15A3 tumor cells (1 × 10⁶ cells/mouse). When tumors were clearly established (~7 days after injection), CAR-engineered CIK cells were intravenously injected (5 × 10⁶ cells/mouse; 4–7 animals/group). The number of CD28-ζ and CD28-ζ–OX40 engineered CIK cells was 16.5 and 19.2%, respectively. (b) Rag^−/− common γ-chain^−/− mice were coinjected with CEA⁺ C15A3 tumor cells (1 × 10⁶ cells/mouse) and CIK cells with or without CAR (2.5 × 10⁵ cells/mouse; 5–7 animals/group). The numbers of injected T cells were adjusted to equal numbers by adding nontransduced CIK cells. Tumor growth was recorded every 2–3 days and the volume was determined using a digital caliper. Mean values are shown; area under the curve (AUC) was calculated and P values were determined using Student's t-test. CEA, carcinoembryonic antigen.