Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response

ABSTRACT

Conditionally replicative adenoviruses represent an innovative group of anticancer agents designed to destroy these cells by replication and lysis. A major problem associated with of the use of adenoviral vectors in gene therapy is its high liver uptake and lack of tumor selectivity upon systemic administration. To improve the efficacy of CRAds as anticancer agents, their infection efficiency on CAR-deficient tumor cells could be enhanced their by redirecting viral entry via a CAR-independent pathway. To redirect the entry pathway of adenoviruses and enhance their infectivity and specificity, two general strategies are being used. In the first strategy, the adenovirus genome is changed to alter the binding specificity of the viral capsid. In the second strategy, a two-component targeted adenovirus is created by binding of proteins with specific affinity for cancer cells onto the viral capsid. Despite effective targeting and tumor eradication in vitro and in mouse models, the results from systemic administration of targeted CrAds is limited. In addition, clinical effects of CrAds are disappointing up till now. Therefore, combination therapies in which targeted CrAds are combined with other types of therapy are being investigated.

Keywords:

Conditionally replicative adenoviruses, targeting, peptides, bispecific single-chain antibodies.