Paramyxovirus Entry and Targeted Vectors for Cancer Therapy

About a century ago, shortly after viruses were recognized, occasional tumor regressions were documented after natural infections. This observation established the idea of using viruses to fight cancer [1]. Early virotherapy clinical trials based on natural viruses were poorly controlled, but recent ones based on modified viruses are subject to extensive monitoring of viral replication, gene expression, and host immunity. Therapeutic efficacy is being assessed by well-defined biological end points, and can be improved [2]. For future clinical trials, more specific and potent oncolytic viruses are being developed based on three principles: targeting, shielding, and arming [3]. Box 1 lists several strategies currently utilized for each category of modification; not all modifications are applicable to all viruses, but interesting combinations of modifications can be applied to many viruses to enhance therapy, as recently discussed [3]. We focus here on the contribution of paramyxoviruses to the development of the next generation of cancer therapeutics, and in particular on targeting viral entry to cancer cells (Box 1, top two lines). We also bring examples of how paramyxovirus envelopes can shield oncolytic viruses from pre-existing antibodies, as well as target viruses of other families, in particular retroand lentiviruses. Finally, we present one example of arming that enhances efficacy of virotherapy through its direct integration into a chemotherapy regimen, locally amplifying its effect. We note that modern virotherapy, while based on the creative application of basic knowledge derived from the study of viruses, is driven by the need for new alternatives for cancer treatment. Thus, while work creating and validating the next generation of vectors progresses, current clinical trials are based on vectors developed 5–10 years ago [4].