1-5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan and arginyl-glycyl-aspartic-acid

The absence or the presence of low levels of the Coxsackievirus and adenovirus receptor (CAR) on several tumor types might limit the efficacy of recently proposed tumor-specific or conditionally replicative adenoviruses (CRAds). To address this issue, we used a genetic modification of the fiber knob in the context of an E1A-defective CRAd to allow CAR-independent target cell infection as a means to enhance oncolytic potency. Such infectivity-enhanced CRAd showed higher replication, more efficient infection, and lysis of tumor cells in vitro. Of note, the improved antitumor effect of the fiber-modified CRAd could be demonstrated in vivo. We conclude that the combination of genomic modification to achieve tumor-selective replication and capsid modification to enhance infectivity yields more potent oncolytic adenoviruses for use in cancer treatment.

Topics: Adenoviridae; Adenovirus E1A Proteins; Animals; Cell Division; Female; Formazans; Genetic Vectors; Humans; Immunologic Tests; In Vitro Techniques; Luciferases; Lung Neoplasms; Male; Mice; Mice, Nude; Oligopeptides; Prostatic Neoplasms; Retinoblastoma Protein; Time Factors; Transplantation, Heterologous; Tumor Cells, Cultured; Virus Replication; Viruses