Genomic diversity and characterization of lungwoms

Analysis of the genetic diversity of organisms plays an important role in research of related species and clinical applications. Lungworms (Dictyocaulus spp) have been identified in many species of ruminants. This study aimed to investigate the genomic variations of lungworms species, which could potentially lead to practical control methods and therapeutics in the distinct species of lungworms. To determine genetic relatedness, lungworm DNA was isolated from white-tailed deer (Odocoileus virginianus), New Zealand Red deer (Cervus elaphus), Louisiana cattle (Bos taurus), Mississippi cattle, and Wisconsin cattle and extracted, amplified through polymerase chain reaction (PCR), and then visualized using agarose gel electrophoresis. Currently, the PCR protocol has been unreliable and protocols are being designed to give more consistent results. At the moment, different approaches are being used to get the PCR to run and be able to get consistent results when amplifying. Once the PCR is fully functional, the next steps will be DNA cloning and sequencing for further investigation of the different species.https://openriver.winona.edu/urc2019/1005/thumbnail.jp

422 Safety and efficacy of neoadjuvant intravesical oncolytic MV-NIS in patients with urothelial carcinoma

BackgroundBladder cancer is a leading cause of cancer death in the United States.1 The histology in > 90% of cases is urothelial carcinoma (UC). Tumors may present either as non-muscle-invasive (NMIBC) or muscle-invasive disease (MIBC). Current standard of care for patients with high risk NMIBC includes transurethral resection of bladder tumor (TURBT) followed by intravesical immunotherapy with Bacillus Calmette-Guerin (BCG).2 Meanwhile, patients with BCG unresponsive NMIBC or MIBC are recommended to undergo radical cystectomy (RC), which adversely impacts quality of life and is associated with significant morbidity.3 MV-NIS is an investigational oncolytic measles virus with an excellent clinical safety profile.4 This ongoing phase I clinical study is designed to test the safety, efficacy and identify the recommended phase 2 dose (RP2D) of intravesical MV-NIS in patients with NMIBC or MIBC who are scheduled for RC and not eligible for neoadjuvant chemotherapy.MethodsBladder UC patients were evaluated for eligibility and provided informed consent prior to enrolling. To date 8 patients have been enrolled: 4 to the single dose safety cohort, and 4 to the multi-dose expansion cohort. Patients were administered intravesical ~1x109 TCID50 MV-NIS once at least 1 week prior to RC (safety cohort), or twice at 4 and 2 weeks prior to RC (expansion cohort). Patients were closely monitored during the 2-hour instillation period. Tumor specimens from the pre-treatment TURBT and post-treatment RC were analyzed to determine pre- and post-treatment pathological stage and evaluate tumor killing and immune cell infiltrate.ResultsIntravesical MV-NIS treatment was well tolerated in all patients. Only a single Adverse Event (AE) attributable to MV-NIS treatment (Grade 1 hematuria). AEs Grade>2 were related to post-surgical complications. Tumor pathology findings are summarized in table 1. Tumor downstaging was observed in 4 of 8 patients. Among 4 patients in the expansion cohort, 2 had no residual disease (pT0). Central assessment of RC tissues showed significant inflammatory infiltrate in all treated bladder specimens. Detailed analyses are ongoing to characterize MV infection and immune infiltrate in bladder tissueAbstract 422 Table 1Pre-treatment (TURBT) and post- treatment (RC) pathologyConclusionsThe higher-than-expected rate of tumor downstaging and pT0 pathology, paired with the significant immune infiltrate observed in post-treatment bladder tissue, provide compelling evidence that intravesical MV-NIS has clinical activity against UC. These results support the use of two doses of ~1x109 TCID50 as the RP2D in future clinical studies for BCG unresponsive NMIBC or MIBC patients. MV-NIS induced inflammation may act synergistically with checkpoint blockade therapies.Trial RegistrationNCT03171493ReferencesSiegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69(1):7–34.Knowles MA, Hurst CD. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer 2015;15(1):25–41.Zakaria AS, Santos F, Dragomir A, Tanguay S, Kassouf W, Aprikian AG. Postoperative mortality and complications after radical cystectomy for bladder cancer in Quebec: A population-based analysis during the years 2000–2009. Can Urol Assoc J 2014;8(7–8):259–267.Galanis E, Atherton PJ, Maurer MJ, Knutson KL, Dowdy SC, Cliby WA, Haluska P Jr, Long HJ, Oberg A, Aderca I, Block MS, Bakkum-Gamez J, Federspiel MJ, Russell SJ, Kalli KR, Keeney G, Peng KW, Hartmann LC. Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer. Cancer Res 2015;75(1):22–30.Ethics ApprovalApproval was received from the Institutional Review boards (IRBs) at all clinical sites including Mayo Clinic (#17–004167); Ochsner Health (#2020 060); and University of Miami (#20200174). All study participants are required to review and sign an IRB approved informed consent before taking part in the clinical trial