PMID- 38101861
OWN - NLM
STAT- MEDLINE
DCOM- 20240110
LR  - 20240110
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 11
IP  - 12
DP  - 2023 Dec 14
TI  - Intravesical Ty21a treatment of non-muscle invasive bladder cancer induces immune 
      responses that correlate with safety and may be associated to therapy potential.
LID - 10.1136/jitc-2023-008020 [doi]
LID - e008020
AB  - BACKGROUND: Standard of care treatment of non-muscle invasive bladder cancer 
      (NMIBC) with intravesical Bacillus Calmette Guerin (BCG) is associated with side 
      effects, disease recurrence/progression and supply shortages. We recently showed 
      in a phase I trial (NCT03421236) that intravesical instillation in patients with 
      NMIBC with the maximal tolerated dose of Ty21a/Vivotif, the oral vaccine against 
      typhoid fever, might have a better safety profile. In the present report, we 
      assessed the immunogenicity of intravesical Ty21a in patients of the clinical 
      trial that had received the maximal tolerated dose and compared it with data 
      obtained in patients that had received standard BCG. METHODS: Urinary cytokines 
      and immune cells of patients with NMIBC treated with intravesical instillations 
      of Ty21a (n=13, groups A and F in NCT03421236) or with standard BCG in a 
      concomitant observational study (n=12, UROV1) were determined by Luminex and flow 
      cytometry, respectively. Serum anti-lipopolysaccharide Typhi antibodies and 
      circulating Ty21a-specific T-cell responses were also determined in the Ty21a 
      patients. Multiple comparisons of different paired variables were performed with 
      a mixed-effect analysis, followed by Sidak post-test. Single comparisons were 
      performed with a paired or an unpaired Student's t-test. RESULTS: As compared 
      with BCG, Ty21a induced lower levels of inflammatory urinary cytokines, which 
      correlated to the milder adverse events (AEs) observed in Ty21a patients. 
      However, both Ty21a and BCG induced a Th1 tumor environment. Peripheral 
      Ty21a-specific T-cell responses and/or antibodies were observed in most Ty21a 
      patients, pointing the bladder as an efficient local immune inductive site. 
      Besides, Ty21a-mediated stimulation of unconventional Vdelta2 T cells was also 
      observed, which turned out more efficient than BCG. Finally, few Ty21a 
      instillations were sufficient for increasing urinary infiltration of dendritic 
      cells and T cells, which were previously associated with therapeutic efficacy in 
      the orthotopic mouse model of NMIBC. CONCLUSIONS: Ty21a immunotherapy of patient 
      with NMIBC is promising with fewer inflammatory cytokines and mild AE, but 
      induction of immune responses with possible antitumor potentials. Future phase II 
      clinical trials are necessary to explore possible efficacy of intravesical Ty21a.
CI  - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published 
      by BMJ.
FAU - Derre, Laurent
AU  - Derre L
AUID- ORCID: 0000-0002-3403-161X
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland 
      Laurent.Derre@chuv.ch.
FAU - Lucca, Ilaria
AU  - Lucca I
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Cesson, Valerie
AU  - Cesson V
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Bohner, Perrine
AU  - Bohner P
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Crettenand, Francois
AU  - Crettenand F
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Rodrigues-Dias, Sonia-Cristina
AU  - Rodrigues-Dias SC
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Dartiguenave, Florence
AU  - Dartiguenave F
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Masnada, Audrey
AU  - Masnada A
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Teixeira-Pereira, Carla
AU  - Teixeira-Pereira C
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Benmerzoug, Sulayman
AU  - Benmerzoug S
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Chevalier, Mathieu F
AU  - Chevalier MF
AUID- ORCID: 0000-0002-5601-2217
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Domingos-Pereira, Sonia
AU  - Domingos-Pereira S
AUID- ORCID: 0000-0003-0784-9464
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Nguyen, Sylvain
AU  - Nguyen S
AUID- ORCID: 0000-0002-6508-1337
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Polak, Lenka
AU  - Polak L
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Schneider, Anna K
AU  - Schneider AK
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Jichlinski, Patrice
AU  - Jichlinski P
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Roth, Beat
AU  - Roth B
AUID- ORCID: 0000-0002-7369-650X
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
FAU - Nardelli-Haefliger, Denise
AU  - Nardelli-Haefliger D
AD  - Urology Research Unit and Urology Biobank, Deptment of Urology, Centre 
      Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20231214
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (BCG Vaccine)
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Adjuvants, Immunologic
MH  - Administration, Intravesical
MH  - BCG Vaccine/adverse effects
MH  - Cytokines
MH  - Immunity
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - *Non-Muscle Invasive Bladder Neoplasms
MH  - *Urinary Bladder Neoplasms/drug therapy/pathology
MH  - Clinical Trials, Phase I as Topic
PMC - PMC10729085
OTO - NOTNLM
OT  - Immunity
OT  - Translational Medical Research
OT  - Tumor Microenvironment
OT  - Urinary Bladder Neoplasms
COIS- Competing interests: DN-H, SD-P and PJ are inventors on patent PCT/EP2014/059392 
      "Salmonella strains for use in the treatment and/or prevention of cancer". The 
      other authors declare no potential conflicts of interest.
EDAT- 2023/12/16 11:43
MHDA- 2023/12/18 06:42
PMCR- 2023/12/14
CRDT- 2023/12/15 20:53
PHST- 2023/11/30 00:00 [accepted]
PHST- 2023/12/18 06:42 [medline]
PHST- 2023/12/16 11:43 [pubmed]
PHST- 2023/12/15 20:53 [entrez]
PHST- 2023/12/14 00:00 [pmc-release]
AID - jitc-2023-008020 [pii]
AID - 10.1136/jitc-2023-008020 [doi]
PST - epublish
SO  - J Immunother Cancer. 2023 Dec 14;11(12):e008020. doi: 10.1136/jitc-2023-008020.