Radio-immunotherapy by 188Re-antiCD20 and stable silencing of IGF-IR in Raji cells, new insight in treatment of lymphoma

Abstract

Abstract Hematologic malignancies such as Non-Hodgkin’s lymphoma (NHL), remain a serious threat to human health due to their heterogeneity and complexity. The inherent genetic heterogeneity of NHL B-cells, as well as the instability of lymphoma cancer cells, results in drug resistance in lymphoma, posing a fundamental challenge to NHL treatment. Burkitt lymphoma (including Raji cell line) is a rare and highly aggressive form of B-cell NHL. Since overexpression of the insulin-like growth factor-1 receptor (IGF-1R) playing a prominent role in the development and transformation of different malignancies, especially lymphoma malignancies, we have explored the role of IGF-1R in the development and progression of Raji cells and the stable silencing of IGF-1R by lentivirus-mediated RNA interference (RNAi). We have shown that stable silencing of the IGF-1R gene in Raji cells using lentivirus-mediated-RNAi have resulted in a significant reduction in Raji cell proliferation. Moreover, the results of the cell viability assays indicated high resistance of Raji cells to rituximab. However, coupling rituximab to 188Re potentially leads to specific targeting of Raji cells by 188Re, improving the therapeutic efficacy. We found that the synergistic effect of using a gene therapy-based system in combination with radioimmunotherapy could be a promising therapeutic strategy in the future. To the best of our knowledge, this is the first study that reports the knock down of IGF-1R via lentiviral-mediated shRNA in Raji cells.