Conditionally replicating adenoviruses for cancer treatment.
Replication-conditional, oncolytic adenoviruses are emerging as powerful tools in the warfare on cancer. The ability to modify cell-specific infectivity or tissue-specific replication machinery, as well as the possibility of modifying viral-cellular protein interactions with cellular checkpoint regulators are emerging as new trends in the design of safer and more effective adenoviruses. The integration of oncolytic adenoviruses with mainstream cancer therapies, such as chemotherapy and radiotherapy, continues to yield significant therapeutic benefits. Adenoviruses can be armed with prodrug-activating enzymes as well as tumor suppressor genes or anti-angiogenic factors, thus providing for enhanced anti-tumor therapy and reduced host toxicity. Thus far, encouraging results have been obtained from extensive preclinical and human clinical studies. However, there is a need to improve adenoviral vectors to overcome unresolved problems facing this promising anti-cancer agent, chief among these issues is the adenovirus-triggered immune response threatening its efficacy. The continued expansion of the knowledge base of adenovirus biology will likely lead to further improvements in the design of the ideal oncolytic adenoviruses for cancer treatment.
Jounaidi
Youssef
Y
Division of Cell and Molecular Biology, Department of Biology, Boston University, Boston, MA 02215, USA. jounaidi@bu.edu
Doloff
Joshua C
JC
Waxman
David J
DJ
D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D000818:Animals; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics / Q000502:physiology*