Expansion of tropism of a feline parvovirus to target a human tumor cell line by display of an αv integrin binding peptide on the capsid

Abstract

The autonomous parvoviruses are small, non-enveloped, single strand DNA viruses. They occur in many species and they have oncolytic properties. We are modifying the capsid of feline panleukopenia virus (FPV), a parvovirus which normally infects feline cells, with the goal of targeting human tumor cells for potential cancer therapy. Using recombinant viruses transducing a luciferase reporter, we show that insertion of a cyclically constrained, integrin-binding peptide at an exposed position on the FPV capsid enables transduction of an ␣v integrin-expressing human rhabdomyosarcoma cell line (Rh18A). These cells were not transduced by virus

Oncolytic viruses in cancer therapy

“…Finally, parvovirus types unable to infect human cells can be used to target human cancer cells by capsid retargeting. For example, a modified feline panleukopenia virus is currently being tested for feasibility as a cancer targeting tool [147].…”

“…In this respect, adenoviruses have undergone the most intensive research and a multitude of adenoviral vectors with altered tropism is available (reviewed in [110]). Retroviruses can be efficiently retargeted to specific cells by pseudotyping them with suitable surface glycoproteins (not just VSV-G) [269] and autonomous parvoviruses can be retargeted by modifying the capsid protein [147] Also, incorporation of tumor-specific peptides into several different gene delivery systems, including viruses, has been shown to significantly augment the targeting of many cancers [270]. For example, the tropism of measles virus has been made strictly cancer cell specific by expression of receptor-binding regions of single-chain antibodies on their surface, which also minimizes infection of non-tumor cells expressing the natural measles receptors CD64 or SLAM (CD150) [271].…”

The Promise of Integrins as Effective Targets for Anticancer Agents

“…This successfully contributed to directing infection of those particles to a human rhabdomyosarcoma cell line [43]. …”

Imaging of Oncolytic Virus Gene Expression

“…It has been used for tracking bacterial pathogens [25], to study gene expression patterns [26], to monitor tumor cell growth and regression [27], to determine the location and proliferation of stem cells [28], and to track gene expression patterns [29]. The luciferase gene has been cloned and used for tracking the replication of oncolytic parvoviruses [30], adenoviruses [31,32], HSV-1 [33,34], vaccinia virus [6,35], measles virus [36], and vesicular stomatitis virus (VSV) [37]. The luciferase gene has been cloned and used for tracking the replication of oncolytic parvoviruses [30], adenoviruses [31,32], HSV-1 [33,34], vaccinia virus [6,35], measles virus [36], and vesicular stomatitis virus (VSV) [37].…”