JCU - Abstracts of the BAUS 2018 Scientific Meeting - June 2018 - 57

Abstracts
Conclusion: BN AUS implantation has a 6% infection/
erosion rate and a 22% chronic infection erosion rate
leading to device explanation. For the 78% of women with
functioning devices, incontinence is cured in 85% and
improved in a further 10%. Only 2 patients remain wet and
both have congenital anatomical abnormalities of the
lower urinary tract.

ePoster Session 6:
Prostate Cancer
Tuesday 26 June
14:00 - 15:45
Room 4
Chairs: Alan Partin & Prasanna
Sooriakumaran
P6-1 An intratumoural cytotopic
immunotherapy approach in a syngeneic
murine model of prostate cancer
Papaevangelou E1, Smolarek D1, Elhage O1, Smith R1,
Dasgupta P1, Galustian C1
1King's College London, United Kingdom

Introduction: The immunosuppressive prostate cancer
microenvironment renders most infiltrating effector
immune cells anergic or regulatory. Immunotherapeutic
agents localised to the prostate can break this immunetolerance leading to greater efficacy and less toxicity than
systemically-administered drugs. We showed previously
that cytotopic modification of interleukin-15 can activate
NK and CD8+ T-cells in the presence of prostate cancer
cells. We now used this cyto-IL-15 and two immunocheckpoint blocking antibodies, which exhibited antitumour response in clinical trials, modified in a similar
approach.
Methods: IL-15 and antibodies were modified by conjugation to a molecule that enables them to adhere to cell
membranes (patents pending), and thus localize to any
potential site of injection. The cytotopically modified
IL-15 and antibodies was injected intratumourally either
alone (cyto-IL-15 or cyto-abs) or in combination (cytocombo) in subcutaneous TRAMP C2 prostate tumours in
C57BL/6 mice and compared with their non-modified
equivalents.
Results: Intratumoural injection of cyto-IL15, combo or
cyto-combo significantly delayed tumour growth at day 14
post-treatment by 45-50%. However, only cyto-IL15 and
cyto-combo significantly increased median survival after
treatment to 28 (p < 0.05) and 24 days (p < 0.05) respectively, compared with 17 days in the control group. Nonmodified IL15 or antibodies alone had no effect on tumour
growth or survival.

57
Conclusion: We have demonstrated that cytotopically
modified immunotherapeutic agents can lead to tumour
growth delay in an in vivo murine model of prostate cancer, induce tumour cell death and increase mouse survival.
This appears to be a promising novel approach for prostate cancer immunotherapy.

P6-2 White blood cells from prostate
cancer patients carry distinct chromosome
conformations
Pchejetski D2, Shah T1,4, Alshaker H5, Ramadass A3,
Hunter E3, Akoulitchev A3, Winkler M1,4
1 Charing Cross Hospital, Imperial College Healthcare NHS
Trust, London, United Kingdom, 2School of Medicine, University
of East Anglia, Norwich, United Kingdom, 3Oxford BioDynamics
Limited, United Kingdom, 4Department of Surgery and
Cancer, Imperial College London, London, United Kingdom,
5 Department of Pharmacology and Biomedical Sciences, Faculty
of Pharmacy and Medical Sciences, Petra University, Amman,
Jordan

Introduction: Current diagnostic blood tests for prostate cancer (PCa) are unreliable for the early stage disease,
resulting in numerous unnecessary prostate biopsies in
men with benign disease and false reassurance of negative
biopsies in men with prostate cancer. In comparison to the
imaging biomarker MRI, which identifies established and
significant prostate cancer we investigate early epigenetic
changes as a diagnostic biomarker.
Methods: We performed chromosome conformation
screening for 14,240 chromosomal loops in the loci of 425
cancer related genes in peripheral blood mononuclear
cells (PBMCs) of n=107 PCa patients and n=105 non-cancer controls. The cancer cohort consisted of all D'Amico
risk groups including metastatic disease.
Results: Our data show that PBMCs from PCa patients
acquire specific chromosome conformation changes in
the loci of cancer-related genes. New chromosomal
loops in the loci of CASP2, ETS1, SLC22A3, MAP3K14
genes were unique to the PCa cohort. Similar chromosomal conformations were identified in primary prostate tumours from these patients, but not in normal
prostate tissues. Blind testing on a validation cohort of
n=10 pts and n=10 controls yielded PCa detection with
80% sensitivity and 80% specificity. Surprisingly, utilising
the signature to predict D'Amico low risk v high risk
disease was also highly accurate (Sensitivity 84%,
Specificity 89%).
Conclusions: We have identified a subset of blood chromosomal conformations that are strongly indicative of
PCa presence and possibly risk of advanced disease.These
signatures have a significant potential for development of a
quick diagnostic blood test for prostate cancer or as a
staging adjunct.

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