Table 1.

Viral Vectors and Cancer Immunotherapy

Viral Vector	Advantages	Disadvantages
Mammalian Poxviruses Vaccinia Virus (VV) Modified virus Ankara (MVA)	Easily manipulated in laboratory setting Accepts large gene inserts Naturally immunogenic Cellular and humoral immune response to transgene Expresses transgenes in target cells, including DC No risk of insertional mutagenesis MVA strain is replication-incompetent	Neutralizing antibodies develop with subsequent vaccinations; recipients of vaccinia (smallpox) vaccine have pre-existing immunity to vector Replication-competent virus (VV), not appropriate for use in immunocompromised patients
Avian Poxvirus Fowlpox Canarypox (ALVAC)	Incomplete lifecycle in mammalian cells, no infectious viral particles can form Multiple vaccinations possible, no neutralizing antibodies develop	Immune response is not as robust as vaccinia virus
Adenovirus (Ad)	Easily manipulated in laboratory setting Cellular and humoral immune response to transgene High expression of transgene Broad tropism, including DC No risk of insertional mutagenesis Many strains available Replication-deficient strains used, limiting pathogenicity	Infection of target cells dependant on express of Ad receptor (e.g. CAR), which is not expressed on all cancer cells Pre-existing host neutralizing antibodies to several Ad serotypes Limited capacity for gene inserts
Alphavirus	Naturally immunogenic High expression of transgene Replicon-competent vector No neutralizing antibodies develop against non- propagating vector Broad tropism Multiple vaccinations possible, no neutralizing antibodies develop	Limited capacity for gene inserts Limited duration of expression of transgene due to induction of apoptosis in infected target cell
Measles Virus (MV)	Specificity for tumor cells Oncolytic virus No risk of insertional mutagenesis Vaccine strain non-pathogenic, non-contagious (Non-pathogenic, does not cause clinical syndrome associated with non-vaccine strain measles infection; Non-contagious, no human-to-human transmission of MV)	Contraindicated in severely immunocompromised patients Pre-existing immunity to MV Modest capacity for gene inserts Viral transgene expression limited by lysis of target cell
Herpes Simplex virus (HSV)	Easily manipulated in laboratory setting Broad tropism, including DC Oncolytic virus Large capacity for gene inserts	Neurotropsim of concern Viral transgene expression limited by lysis of target cell
Vesicular stomatitis virus	Broad tropism, including DC High efficacy of gene expression No risk of insertional mutagenesis Vaccine strain non-pathogenic, non-contagious Oncolytic virus Enhances immune-mediated attack of tumor cells	Neurotropsim of concern Modest capacity for gene inserts Viral transgene expression limited by lysis of target cell

DC – Dendritic cells

CAR – Coxsackie and adenovirus receptor