Cancer immunotherapy using sindbis virus replicon particles encoding a VP22-antigen fusion

Wen Fang Cheng, Chien Fu Hung, Keng Fu Hsu, Chee Yin Chai, Liangmei He, John M. Polo, Leigh A. Slater, Morris Ling, T. C. Wu

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)553-568
Number of pages16
JournalHuman Gene Therapy
Volume13
Issue number4
DOIs
Publication statusPublished - 2002 Mar 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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