Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded

Top Cited Papers
Open Access
Publisher Website
Google Scholar
Abstract
Viruses are reprogrammed into vectors for cancer treatment based on three types of modification: targeting, arming and shielding. Viruses that are turned into therapeutics are beginning to find their place in cancer clinical practice, in combination with chemotherapy and radiation. The principles of virus reprogramming are illustrated in this article using adenovirus, a DNA virus with a naked icosahedral capsid, and measles virus, an enveloped RNA virus with a helical capsid. Targeting introduces multiple layers of cancer specificity, thereby improving safety and efficacy. The four basic layers of specificity are: particle activation through cancer-specific proteases; cell entry through cancer-specific cell-surface proteins; control of viral transcription and replication by tissue-specific promoters; and preferential spread of viruses that exploit cancer-specific molecular defects. Arming occurs through genes that express prodrug convertases, pro-apoptotic proteins or immuno-activating proteins. Coating with polymers and sequential usage of different envelopes or capsids provides shielding from the host immune response. The window of therapeutic opportunity can be extended by temporary immunosuppression. A five-step plan to turn a virus of choice into a potential oncolytic is discussed.