TY  - JOUR
A1  - Ardelt, Peter U.
A1  - Ebbing, Jan
A1  - Adams, Fabian
A1  - Reiss, Cora
A1  - Arap, Wadih
A1  - Pasqualini, Renata
A1  - Bachmann, Alexander
A1  - Wetterauer, Ulrich
A1  - Riedmiller, Hubertus
A1  - Kneitz, Burkard
T1  - An anti-ubiquitin antibody response in transitional cell carcinoma of the urinary bladder
JF  - PLoS ONE
N2  - Background 
To use combinatorial epitope mapping ("fingerprinting") of the antibody response to identify targets of the humoral immune response in patients with transitional cell carcinoma (TCC) of the bladder. 

Methods 
A combinatorial random peptide library was screened on the circulating pool of immunoglobulins purified from an index patient with a high risk TCC (pTa high grade plus carcinoma in situ) to identify corresponding target antigens. A patient cohort was investigated for antibody titers against ubiquitin. 

Results 
We selected, isolated, and validated an immunogenic peptide motif from ubiquitin as a dominant epitope of the humoral response. Patients with TCC had significantly higher antibody titers against ubiquitin than healthy donors (p<0.007), prostate cancer patients (p<0.0007), and all patients without TCC taken together (p<0.0001). Titers from superficial tumors were not significantly different from muscle invasive tumors (p = 0.0929). For antibody response against ubiquitin, sensitivity for detection of TCC was 0.44, specificity 0.96, positive predictive value 0.96 and negative predictive value 0.41. No significant titer changes were observed during the standard BCG induction immunotherapy. 

Conclusions 
This is the first report to demonstrate an anti-ubiquitin antibody response in patients with TCC. Although sensitivity of antibody production was low, a high specificity and positive predictive value make ubiquitin an interesting candidate for further diagnostic and possibly immune modulating studies.
KW  - Bacillus-Calmette-Guerin
KW  - immune response
KW  - ubiquitin
KW  - protein biomarkers
KW  - system bcg
KW  - tumor cells
KW  - immunotherapy
KW  - cancer surveillance
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143711
VL  - 10
IS  - 3
ER  - 
TY  - JOUR
A1  - D'Andrea, David
A1  - Soria, Francesco
A1  - Grotenhuis, Anne J.
A1  - Cha, Eugene K.
A1  - Malats, Nuria
A1  - Di Stasi, Savino
A1  - Joniau, Steven
A1  - Cai, Tommaso
A1  - Rhijn, Bas W. G. van
A1  - Irani, Jaques
A1  - Karnes, Jeffrey
A1  - Varkarakis, John
A1  - Baniel, Jack
A1  - Palou, Joan
A1  - Babjuk, Marek
A1  - Spahn, Martin
A1  - Ardelt, Peter
A1  - Colombo, Renzo
A1  - Serretta, Vincenzo
A1  - Dalbagni, Guido
A1  - Gontero, Paolo
A1  - Bartoletti, Riccardo
A1  - Larré, Stephane
A1  - Malmstrom, Per-Uno
A1  - Sylvester, Richard
A1  - Shariat, Shahrokh F.
T1  - Association of patients’ sex with treatment outcomes after intravesical bacillus Calmette–Guérin immunotherapy for T1G3/HG bladder cancer
JF  - World Journal of Urology
N2  - Purpose
To investigate the association of patients’ sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette–Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC).

Materials and methods
We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients’ sex with HG-recurrence and disease progression.

Results
A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01–1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92–1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients’ sex was not associated with recurrence (HR 0.99, 95%CI 0.80–1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78–1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78–1.60, p = 0.55).

Conclusion
Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.
KW  - bladder cancer
KW  - BCG
KW  - response
KW  - age
KW  - progression
KW  - recurrence
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-344486
VL  - 39
IS  - 9
ER  -