Secretion of IFN-gamma Angiogenesis inhibitor and IL-2 T cells co-cultured with Raji cells could induce a sustaining secretion of IFN-gamma in a time-dependent manner. Comparing to control and blank group, IFN-gamma secreted in experimental group had an express go up at 12-hour time point and was obvious superior in subsequent time points (Fig. 3A). Figure 3

A: Raji cells were co-cultured with anti-CD20scFvFc/CD28/CD3ζ, anti-CD20scFvFc transduced T cells or untransduced T cells. Supernatants from these cultures were tested by ELISA for IFN-gama. B: Supernatants from these cultures were tested by ELISA for IL-2. C: AP-1 DNA binding were measured by EMSA. (In experimental group, *represents p < 0.05 compared to control group at the same time point). As the time go by, the secretion of IL-2 in supernatant of experimental group had an obvious increase trend. It had obvious superior statistically significant differences compared to other two groups from initial co-culture (Fig. 3B). AP-1 binding in gene modified T cells Due to it has been demonstrated that there is a strong cooperativity between transcription factors that

bind to the IL-2 promoter, in particular, activating protein 1 (AP-1) in regulating IL-2 transcription. To determine if gene modified T cells increase IL-2 secretion levels by altering the DNA binding activity of the transcription factor, AP-1, EMSA analysis Protein Tyrosine Kinase inhibitor was performed. Our results demonstrated that gene modified T cells altered the DNA binding activity of AP-1. AP-1 binding in gene modified T cells of experimental group had distinctly superior compared to control group (Fig. 3C). Discussion The anti-CD20 monoclonal Cediranib antibody has demonstrated its efficacy in non-Hodgkin’s lymphoma treatment. However, despite the success of Rituximab treatment, resistance resulting to non-response to treatment or early relapse of the original disease occurs in around 50% of the patients [7]. Although the precise mechanism of resistance to Rituximab Isotretinoin is not

fully understood, it is suggested that the patient-specific microenvironment of the lymphoma is related to cancer resistance. The significance of the microenvironment in Rituximab-induced cell death is indirectly observed by differential responses to Rituximab therapy in different subtypes of CD20-positive lymphomas (which have unique microenvironments) [7]. Malignant tumor cells can receive additional survival signals in some unique microenvironments, as some lymph node compartments (germinal centres) [3, 8]. Moreover, the myeloid-lineage cells infiltrating some of these lymphomas may provide trophic stimuli to the malignant cells [9]. Exposure to these pro-survival signals makes these cells less sensitive to the anti-CD20 antibody. Accordingly, attempts have been made to improve the therapeutic efficacy and overcome some resistance. For example, combination therapy is a method to overcome some resistance to regular chemotherapy in some patients who over-express Bcl-2 [10].