Cancer immunotherapy using sindbis virus replicon particles encoding a VP22-antigen fusion
Journal
Human Gene Therapy
Journal Volume
13
Journal Issue
4
Pages
553-568
Date Issued
2002
Author(s)
Abstract
Alphavirus vectors have emerged as a strategy for the development of cancer vaccines and gene therapy applications. The availability of a new packaging cell line (PCL), which is capable of generating alphavirus replicon particles without contamination from replication-competent virus, has advanced the field of vaccine development. This replication-defective vaccine vector has potential advantages over naked nucleic acid vaccines, such as increased efficiency of gene delivery and large-scale production. We have developed a new strategy to enhance nucleic acid vaccine potency by linking VP22, a herpes simplex virus type 1 (HSV-1) tegument protein, to a model antigen. This strategy facilitated the spread of linked E7 antigen to neighboring cells. In this study, we created a recombinant Sindbis virus (SIN)-based replicon particle encoding VP22 linked to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, using a stable SIN PCL. The linkage of VP22 to E7 in these SIN replicon particles resulted in a significant increase in the number of E7-specific CD8+ T cell precursors and a strong antitumor effect against E7-expressing tumors in vaccinated C57BL/6 mice relative to wild-type E7 SIN replicon particles. Furthermore, a head-to-head comparison of VP22-E7-containing naked DNA, naked RNA replicons, or RNA replicon particle vaccines indicated that SINrep5-VP22/E7 replicon particles generated the most potent therapeutic antitumor effect. Our results indicated that the VP22 strategy used in the context of SIN replicon particles may facilitate the generation of a highly effective vaccine for widespread immunization.
SDGs
Other Subjects
cancer vaccine; CD8 antigen; naked DNA; RNA; tumor antigen; virus vector; Alpha virus; animal cell; antineoplastic activity; article; cancer immunotherapy; cell line; controlled study; DNA replication; gene targeting; Herpes simplex virus 1; immunization; mouse strain; nonhuman; packaging; replicon; RNA replication; Sindbis virus; stem cell; T lymphocyte; vaccination; viral contamination; virus recombinant; virus replication; Wart virus; Animals; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Gene Transfer Techniques; Immunotherapy; Mice; Mice, Inbred C57BL; Neoplasms; Oncogene Proteins, Viral; Replicon; Sindbis Virus; Vaccines, DNA; Viral Proteins; Alphavirus; Animalia; Human herpesvirus 1; Human papillomavirus; Human papillomavirus type 16; Human papillomavirus types; Papillomavirus; Simplexvirus; Sindbis virus
Type
journal article