Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy.
Intravesical instillation of Bacillus Calmette-Guérin is currently used as adjuvant therapy for superficial, non-muscle invasive bladder cancer (NMIBC). However, nearly 40% of patients with NMIBC will fail Bacillus Calmette-Guérin therapy. In an attempt to investigate the feasibility of using insect baculovirus-based vectors for bladder cancer therapy, we observed that intravesical instillation of baculoviruses without transgene up-regulated a set of Th1-type of cytokines and increased the survival rate of mice bearing established orthotopic bladder tumors. When baculoviral vectors were used to co-deliver the mouse CD40 ligand and IL-15 genes through intravesical instillation, the immunogene therapy triggered significantly increased bladder infiltrations of inflammatory monocytes, CD4(+), CD8(+) and γδ T lymphocytes. All treated animals survived beyond 12 months whereas control animals died around 2 months after tumor inoculation. We conclude that direct intravesical instillation of baculoviral gene transfer vectors holds the potential to be a novel therapeutic modality for NMIBC.
Department of Biological Sciences, National University of Singapore, 117543 Singapore.|Institute of Bioengineering and Nanotechnology, 138669 Singapore.
Wei Xia
WX
Ang
Institute of Bioengineering and Nanotechnology, 138669 Singapore.
Ying
Y
Zhao
Tessa Therapeutics, 239351 Singapore.
Timothy
T
Kwang
Institute of Bioengineering and Nanotechnology, 138669 Singapore.|Tessa Therapeutics, 239351 Singapore.
Chunxiao
C
Wu
Tessa Therapeutics, 239351 Singapore.
Can
C
Chen
Division of Medical Oncology, National Cancer Centre, 169610 Singapore.
Han Chong
HC
Toh
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119074 Singapore.
Ratha
R
Mahendran
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119074 Singapore.
Kesavan
K
Esuvaranathan
Department of Biological Sciences, National University of Singapore, 117543 Singapore.|Institute of Bioengineering and Nanotechnology, 138669 Singapore.
Shu
S
Wang
D000818:Animals; D016367:Baculoviridae / Q000502:physiology*; D045744:Cell Line, Tumor; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D050130:Oncolytic Virotherapy; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*