Management of BCG Recurrent Bladder Cancer

Downs, Tracy M.; Lee, Dong Hoon; Scherr, Douglas

doi:10.1007/978-1-4939-1881-2_20

Cited by 1 publication

(1 citation statement)

References 109 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is no evidence to suggest that BCG generates protective anti‐tumor immunity and this may partly explain the high rate of treatment failure (Biot et al , ). In fact, there has been very little improvement in the treatment of high‐grade NMIBC in the last 10–20 years and recurrence after BCG therapy is still one of the most significant problems in the management of bladder cancer (Downs et al , ). This highlights the urgent need for safer and more reliable bladder‐sparing approaches.…”

Section: Introductionmentioning

confidence: 99%

Deletion of F4L (ribonucleotide reductase) in vaccinia virus produces a selective oncolytic virus and promotes anti‐tumor immunity with superior safety in bladder cancer models

et al. 2017

View full text Add to dashboard Cite

Bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. In particular, standard of care for high‐grade disease, Bacillus Calmette–Guérin (BCG), fails in 30% of patients. We have generated a novel oncolytic vaccinia virus (VACV) by mutating the F4L gene that encodes the virus homolog of the cell‐cycle‐regulated small subunit of ribonucleotide reductase (RRM2). The F4L‐deleted VACVs are highly attenuated in normal tissues, and since cancer cells commonly express elevated RRM2 levels, have tumor‐selective replication and cell killing. These F4L‐deleted VACVs replicated selectively in immune‐competent rat AY‐27 and xenografted human RT112‐luc orthotopic bladder cancer models, causing significant tumor regression or complete ablation with no toxicity. It was also observed that rats cured of AY‐27 tumors by VACV treatment developed anti‐tumor immunity as evidenced by tumor rejection upon challenge and by ex vivo cytotoxic T‐lymphocyte assays. Finally, F4L‐deleted VACVs replicated in primary human bladder cancer explants. Our findings demonstrate the enhanced safety and selectivity of F4L‐deleted VACVs, with application as a promising therapy for patients with BCG‐refractory cancers and immune dysregulation.

show abstract

Section: Introductionmentioning

confidence: 99%