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Oncolytic adenoviruses for targeted cancer therapy: From the laboratory to the clinic
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Abstract:
Extensive investigations of oncolytic adenoviruse (OA) from the laboratory to the clinic have been made in the past decades. There are a few strategies for improving the potential targeted therapy of OA in cancer, including transcriptional targeting by mutating functional genes (such as E1A or E1B ) of Ad genome which is involved in the control of cell cycle checkpoints in cells and/or utilizing tumor-specific promoter control of E1A expression, transductional targeting by changing tropism of OA with different types or incorporated by RGD motif into tumor cells, and cell carriers for delivery of OA to the distant tumor sites. Enhanced anti-tumor immune response, apoptosis or suicide of tumor cells elicited by OA, as vector, enabling express immunoregulatory or therapeutic genes contribute to generate synergetic antitumor effects with OA. Clinical trials of OA for various solid tumors have been carried out, in which the application for patients is safe, presenting well tolerated, mild to moderate adverse events, though few objective tumor responses to patients have been observed. Combination of OA with other therapies, such as chemotherapy or radiotherapy can improve clinical efficacy. Future directions of OA development should be focus on strengthening the research on OA-associated immunological mechanisms, breaking through some technical bottlenecks hampering deep studies of OA, optimizing cell carries for targeting of OA to distant tumor sites, and looking for more potential targets such cancer stem cells. In addition, enlarging the range of clinical OA trials and reinforcing the investigations to combine OA with other therapeutic approaches, particularly with immunotherapy, are needed.
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Project Supported:
Project supported by National Natural Science Foundation of China (No. 30972804, No.81172162)
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