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Intravesical oncolytic viral therapy using attenuated, replication‐competent, herpes simplex viruses G207 and Nv1020 is effective in the treatment of bladder cancer in an orthotopic syngeneic model
Author(s) -
Cozzi Paul J.,
Malhotra Sandeep,
McAuliffe Priscilla,
Kooby David A.,
Federoff Howard J.,
Huryk Bob,
Johnson Paul,
Scardino Peter T.,
Heston Warren D.W.,
Fong Yuman
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0533fje
Subject(s) - oncolytic virus , herpes simplex virus , medicine , viral therapy , hsl and hsv , virology , bladder cancer , antiviral therapy , cancer , cancer research , immunology , virus , pathology , disease , infectious disease (medical specialty) , covid-19 , chronic hepatitis
Attenuated, replication‐competent herpes simplex virus mutants are attracting interest because of their ability to replicate within and kill tumor cells while remaining of low pathogenicity to normal tissues. In this study we investigated the ability of two oncolytic candidates, G207 and NV1020, to infect and lyse human and murine transitional cell carcinoma (MBT‐2) cells in vitro and their in vivo efficacy in a well‐established immunocompetent animal model of bladder cancer. Both viruses were effective at infecting, replicating within, and achieving subsequent cell lysis for all four human bladder cancer cell lines and MBT‐2. We found a strong correlation between infection efficiency and subsequent cell death. In vivo studies demonstrated that these viruses were effective with a single intravesical instillation and even more effective with multiple instillations at reducing tumor burden and achieving cures of orthotopic bladder cancer in syngeneic C3h/Hej mice. Immunohistochemistry and histological studies demonstrated that viral replication and cell death were restricted to bladder cancer cells. These results suggest that both G207 and NV1020 hold particular promise for intravesical treatment of human bladder cancer and that ease of intravesical instillation facilitates efficient delivery of virus to tumor cells.