A promising combination strategy: oncolytic adenovirus (ΔE1B-55 K/E3) and arsenic trioxide for potent cancer therapy

Oncolytic adenovirus has emerged as a promising tool in cancer therapy due to its ability to infect and proliferate preferentially within tumor cells. However, due to its insufficient antitumor activity for effective tumor elimination, various approaches, including combination with chemotherapeutic drugs, have been employed to enhance its efficacy. In this study, we aimed to develop an oncolytic adenovirus, termed Oncomed, with a deletion in the E1B-55 K/E3 genes, and then boost its virotherapeutic efficacy by co-treatment with arsenic trioxide (ATO). We proposed that combining Oncomed with ATO might produce synergistic anticancer effects, thereby potentially reducing systemic toxicity and increasing the therapeutic index. Oncomed has demonstrated that it specifically targets and lyses cancer cells, irrespective of their p53 status, while sparing normal cells. Through in vitro assays, we examined the effects of the combination therapy of oncomed and ATO on various cell lines, including U87MG, A549, HT29, MCF7, and TSCC, and observed a pronounced synergistic effect in the U87MG cell line. Subsequently, the cell cycle and apoptosis assays supported the MTT results. Additionally, this study assessed the therapeutic efficacy of the combination in vivo using glioblastoma (U87 MG) xenograft models, demonstrating significant tumor growth suppression, particularly in advanced-stage tumors. Histopathological analysis showed that the combination group had less cell proliferation (as evidenced by reduced Ki-67 expression) and greater tumor necrosis. This study reveals the synergistic effects of Oncomed and ATO, suggesting a potential combinatorial strategy to address the limitations of current cancer treatments and improve patient outcomes.