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Publication
Intravesical Anti-PD-1 Immune Checkpoint Inhibition Treats Urothelial Bladder
Cancer in a Mouse Model.
Authors Kirschner AN, Wang J, Rajkumar-Calkins A, Neuzil KE, Chang SS
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal The Journal of urology
Year 2021
Date Published 5/1/2021
Volume : Pages 205 : 1336 - 1343
PubMed Reference 33356477
Abstract Nonmuscle-invasive bladder cancer is treated by resection within the bladder and
bladder instillment with bacillus Calmette-Guérin or chemotherapy. For bacillus
Calmette-Guérin-refractory disease, systemic anti-PD-1 (programmed cell death
protein 1) immune checkpoint inhibition is a treatment. Our aim is to test
whether intravesical instillment with anti-PD-1 inhibitor treats localized
bladder cancer as effectively as systemic administration., We investigated an
orthotopic mouse model of urothelial bladder cancer using MBT2 cells instilled
into the bladders of syngeneic, wild-type C3H mice. Groups of 10 mice received
each treatment for comparison of intravesical anti-PD-1, intraperitoneal
anti-PD1, and intravesical chemotherapy. The primary outcome was overall
survival and secondary outcomes included long-term immunity and toxicity.,
Anti-PD-1 administered by bladder instillment (intravesical route) successfully
treats localized bladder cancer and has similar overall survival to anti-PD-1 by
systemic route. Anti-PD-1 by either route provides a significant survival
advantage over control antibody. Anti-PD-1 increases CD8+ cell infiltration in
tumors, particularly when administered intravesically. Antibody treatment avoids
toxicity observed for intravesical chemotherapy. Mice who cleared their tumors
after initial treatment were rechallenged with tumor engraftment 3-9 months
later without any additional treatment. Initial anti-PD-1-treated mice did not
grow tumors when rechallenged, which suggests long-term immunity exists, but
initial mitomycin-treated mice readily grew tumors indicating no immunity
occurred by chemotherapy treatment., Intravesical administration of anti-PD-1 is
a promising treatment route for localized bladder cancer, with comparable
overall survival to systemic anti-PD-1 in this mouse model. Intravesical
anti-PD-1 increases CD8+ T cells in treated tumors and long-term immunity was
seen to tumor rechallenge.




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