Medical Specialties Commons^™

The Critical Need For Mental Health Education To Be Mandated In New Mexico's Public Schools, Bonnie L. Murphy

Shared Knowledge Conference

Based on a review of research and best practices in mental health awareness and skills, this inquiry project argues for state legislative policies that would require mental health awareness and skills in the K-12 curriculum. Mental health affects individual accomplishments in every stage of people’s lives beginning in early childhood and throughout the life cycle. Prevention and treatment of mental illness plays a key role in the ability of an individual to cope with loss and develop resiliency and perseverance in challenging times and to make better decisions that improve the individual’s life and the lives of those around them. …

Initiating Patient Discussions About Oocyte Cryopreservation: Attitudes Of Obstetrics And Gynaecology Resident Physicians, Brennan Peterson, C. Gordon, Julia K. Boehm, M. C. Inhorn, P. Patrizio

Marriage and Family Therapy Faculty Articles and Research

This study examined the attitudes of obstetrics and gynaecology (OB/GYN) resident physicians to initiating patient discussions regarding medical and elective oocyte cryopreservation (OC). The study used a cross-sectional online survey of OB/GYN medical residents in the USA, sampled from residency programmes approved by the American Council for Graduate Medical Education. In total, 208 medical residents, distributed evenly between postgraduate years 1–4, participated in the study. Residents' fertility knowledge and attitudes to initiating discussions about OC were gathered. Forty percent (n = 83) believed that OB/GYN residents should initiate discussions about OC with patients (initiators), while 60% (n = 125) did …

Comparison Of Outcomes For Supine Vs. Prone Position Ercp: A Systematic Review And Meta-Analysis, Harmeet Singh Mashiana, Mahendran Jayaraj, Babu Pappu Mohan, Gordon Ohning, Douglas G. Adler

School of Medicine Faculty Research

Background While endoscopic retrograde cholangiopancreatography (ERCP) is usually performed in the prone position, some studies have advocated for ERCP in the supine position. Studies comparing the technical success and safety outcomes have shown variable results. We performed a systematic review and meta-analysis of studies reporting the comparison between the two positions for ERCP outcomes. Methods We conducted a search of electronic databases and conference proceedings including PubMed, EMBASE, and Web of Science databases (from inception through October 2016) to identify studies that reported the comparison of technical success and safety outcomes between supine and prone ERCP. The primary outcome was …

One-Day Oral Polyethylene Glycol Based Cleanout Is Effective For Pre-Colonoscopy Preparation In Children., Ashwath S. Kumar, Brooke L. Beutler, Thomas M. Attard

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The adequacy of pre-procedure preparation is the principal determinant of the quality of colonoscopy in pediatric as in adult patients. There is a lack of consensus, among providers on a standard pre-procedure regimen. Professional society guidelines include the use of Polyethylene glycol (PEG). Herein we report on the provider-assessed adequacy of a one day, age-categorized dosing, PEG based cleanout regimen in children undergoing colonoscopy in a tertiary institution.

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METHODS: The standard bowel preparation regime at our institution includes an age dependent minimum PEG dosing regimen in addition to clear liquids the day prior to the procedure. We retrospectively …

How Younger Adults With Psychosocial Problems Experienced Person-Centered Health Consultations, Line Soot, Kirsten S. Freund, Jørgen Lous, Mikkel Vass, Lotte Hvas

Patient Experience Journal

Much attention is focused on the social determinants of health. Family medicine is challenged with a growing number of vulnerable persons with psychosocial or lifestyle related problems. The objective of this work was to explore how vulnerable younger adults experience person-centered preventive health consultations with their general practitioner. The design and setting for this work were a secondary qualitative analysis of a randomized controlled trial (RCT) in Danish general practices. Younger adults (20-45) were consecutively invited to answer a screening questionnaire about psychosocial and lifestyle-related problems when visiting general practice (28 general practitioners (GPs)) for ordinary consultations. The 30% most …

The Perioperative Patient Experience Of Hand And Wrist Surgical Patients: An Exploratory Study Using Patient Journey Mapping, Else F. De Ridder, Tessa Dekkers, Jarry T. Porsius, Gerald Kraan, Marijke Melles

Patient Experience Journal

Patient-centred care is becoming more important in healthcare. The success of patient-centred care can be assessed by exploring the patient experience through a patient journey map. As the number of outpatient surgeries is increasing, it is important to reveal the specific characteristics of this type of surgery. The perioperative patient experience is considered very important for outpatient surgery, because all perioperative activities are condensed in one day. To investigate this experience, we performed a case study of hand and wrist surgery. Six teams of two industrial design engineering students interviewed 40 patients in total in two private and two public …

Patients Educating Health Care Providers On Lynch Syndrome, Kelsey Hennig, Barry Decoster, Rebecca Chu, Wendy Parker, Lisa Campo-Engelstein, Allison M. Burton-Chase

Patient Experience Journal

Objective: Lynch syndrome (LS) patients are at an elevated risk for early-onset cancers, including endometrial and colorectal (CRC). Prior research has shown a deficit in provider knowledge of LS, which may affect patient satisfaction and adherence to recommended screening and surveillance regimens. Studies suggest patients with LS may educate providers perceived as lacking LS knowledge; however, little is known about these interactions. The goal of this study is to assess patient-reported outcomes from clinical interactions where LS patients educate their providers.

Methods: Participants (n=55) were asked to complete an in-depth telephone interview.

Results: Out of 55 participants, …

Epigenetic Profiling For The Molecular Classification Of Metastatic Brain Tumors., Javier I Orozco, Theo A Knijnenburg, Ayla O Manughian-Peter, Matthew P Salomon, Garni Barkhoudarian, John R Jalas, James S Wilmott, Parvinder Hothi, Xiaowen Wang, Yuki Takasumi, Michael E Buckland, John F Thompson, Georgina V Long, Charles S Cobbs, Ilya Shmulevich, Daniel F Kelly, Richard A Scolyer, Dave S B Hoon, Diego M Marzese

Articles, Abstracts, and Reports

Optimal treatment of brain metastases is often hindered by limitations in diagnostic capabilities. To meet this challenge, here we profile DNA methylomes of the three most frequent types of brain metastases: melanoma, breast, and lung cancers (n = 96). Using supervised machine learning and integration of DNA methylomes from normal, primary, and metastatic tumor specimens (n = 1860), we unravel epigenetic signatures specific to each type of metastatic brain tumor and constructed a three-step DNA methylation-based classifier (BrainMETH) that categorizes brain metastases according to the tissue of origin and therapeutically relevant subtypes. BrainMETH predictions are supported by routine histopathologic evaluation. …

Brain Metastasis Dna Methylomes, A Novel Resource For The Identification Of Biological And Clinical Features., Matthew P Salomon, Javier I J Orozco, James S Wilmott, Parvinder Hothi, Ayla O Manughian-Peter, C Cobbs, Richard A Scolyer, Dave S B Hoon, Diego M Marzese

Articles, Abstracts, and Reports

Brain metastases (BM) are one the most lethal and poorly managed clinical complications in cancer patients. These secondary tumors represent the most common intracranial neoplasm in adults, most frequently originating from lung cancer, breast cancer, and cutaneous melanoma. In primary brain tumors, such as gliomas, recent advances in DNA methylation profiling have allowed for a comprehensive molecular classification. Such data provide prognostic information, in addition to helping predict patient response to specific systemic therapies. However, epigenetic alterations of metastatic brain tumors with specific biological and translational relevance still require much further exploration. Using the widely employed Illumina Infinium HumanMethylation 450K …

Dual-Display Laparoscopic Laser Speckle Contrast Imaging For Real-Time Surgical Assistance, Jaepyeong Cha, Corey Zheng, Lung Wai Lau

Pediatrics Faculty Publications

Laser speckle contrast imaging (LSCI) utilizes the speckle pattern of a laser to determine the blood flow in tissues. The current approaches for its use in a clinical setting require a camera system with a laser source on a separate optical axis making it unsuitable for minimally invasive surgery (MIS). With blood flow visualization, bowel viability, for example, can be determined. Thus, LSCI can be a valuable tool in gastrointestinal surgery. In this work, we develop the first-of-its-kind dual-display laparoscopic vision system integrating LSCI with a commercially available 10mm rigid laparoscope where the laser has the same optical axis as …

Tri-Ponderal Mass Index In Survivors Of Childhood Brain Tumors: A Cross-Sectional Study., E Danielle Sims, Kuan-Wen Wang, Adam Fleming, Donna L Johnston, Shayna M Zelcer, Shahrad Rod Rassekh, Sarah Burrow, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

Survivors of childhood brain tumors (SCBT) face a higher risk of cardiometabolic disorders and premature mortality compared to the general population. Excess adiposity is a known risk factor for these comorbidities. However, while SCBT have higher adiposity compared to healthy controls, measuring adiposity in clinical practice involves access to specialized equipment and may impact busy clinical services. Tri-ponderal Mass Index (TMI; kg/m

A Randomized Control Trial Of Anti-Inflammatory Regional Hypothermia On Urinary Continence During Robot-Assisted Radical Prostatectomy., Linda M Huynh, Douglas Skarecky, James R Porter, Christian Wagner, Jorn Witt, Timothy Wilson, Clayton Lau, Thomas E Ahlering

Articles, Abstracts, and Reports

The present study seeks to present a single-blind, randomized control trial of a hypothermic anti-inflammatory device, the endorectal cooling balloon (ECB), to assess whether regional hypothermia could improve 90-day and time to pad-free continence following robot-assisted radical prostatectomy (RARP). Five high-volume surgeons at three institutions had patients randomized (1:1) to regional hypothermia with ECB versus control. Patients were blinded to device use, as it was inserted and removed intraoperatively. Knowledge of device use was restricted to the operating room personnel only; recovery room and ward nursing staff were not informed of device use and instructed to indicate such if a …

Serous Cystadenoma Of Pancreas : A Clinicopathologic Experience Of 23 Cases From A Major Tertiary Care Center, Muhammad Usman Tariq, Zubair Ahmad, Jamshid Abdul Ghafar, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Background: Serous cystadenomas of pancreas are rare benign epithelial neoplasms, which predominantly occur in the pancreatic body and tail of elderly females. Majority of these tumors have microcystic appearance. Macrocystic and solid variants have also been described. A number of more aggressive cystic pancreatic lesions are included in the differential diagnosis. Distinction from such lesions is important for optimal management.
Objective: Our aim was to study the clinical and histological features of serous cystadenomas which would be helpful in making their correct diagnosis and understanding their behavior.
Methods: We reviewed 23 cases of serous cystadenomas diagnosed in our institution between …

Restoration Of Left Ventricular Function Following Lvad Implantation – Remission Or Recovery? A Case Series., Shiksha Joshi, Mariah Barlow, Maya Guglin

The VAD Journal

Background

A wide range of left ventricular (LV) recovery rates on left ventricular assist device (LVAD) support have been reported. In this case series, we summarize our experience with LVAD explantation for presumed LV recovery.

Case series

Out of 240 patients who received an LVAD implant in our program since its inception, we explanted/inactivated the pump for presumed LV recovery in only three patients. All three of these patients had relapse of cardiomyopathy within 6 months of explantation.

Conclusion

Our experience does not support the existence of LV recovery following LVAD implantation as a common phenomenon. Improvement in LV function …

Performance Of Prostate Cancer Recurrence Nomograms By Obesity Status: A Retrospective Analysis Of A Radical Prostatectomy Cohort., Charnita Zeigler-Johnson, Aaron Hudson, Karen Glanz, Elaine Spangler, Knashawn H Morales

Department of Medical Oncology Faculty Papers

BACKGROUND: Obesity has been associated with aggressive prostate cancer and poor outcomes. It is important to understand how prognostic tools for that guide prostate cancer treatment may be impacted by obesity. The goal of this study was to evaluate the predicting abilities of two prostate cancer (PCa) nomograms by obesity status.

METHODS: We examined 1576 radical prostatectomy patients categorized into standard body mass index (BMI) groups. Patients were categorized into low, medium, and high risk groups for the Kattan and CaPSURE/CPDR scores, which are based on PSA value, Gleason score, tumor stage, and other patient data. Time to PCa recurrence …

Oral Ondansetron Administration To Nondehydrated Children With Diarrhea And Associated Vomiting In Emergency Departments In Pakistan: A Randomized Controlled Trial, Stephen B. Freedman, Sajid Bashir Soofi, Andrew R. Willan, Sarah Williamson Urquhart, Noshad Ali, Jianling Xie, Fady Dawoud, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Study objective: We determine whether single-dose oral ondansetron administration to children with vomiting as a result of acute gastroenteritis without dehydration reduces administration of intravenous fluid rehydration.
Methods: In this 2-hospital, double-blind, placebo-controlled, emergency department–based, randomized trial conducted in Karachi Pakistan, we recruited children aged 0.5 to 5.0 years, without dehydration, who had diarrhea and greater than or equal to 1 episode of vomiting within 4 hours of arrival. Patients were randomly assigned (1:1), through an Internet-based randomization service using a stratified variable-block randomization scheme, to single-dose oral ondansetron or placebo. The primary endpoint was intravenous rehydration (administration of 20 …

Validation Of Near Infrared Fluorescence (Nirf) Probes In Vivo With Dual Laser Nirf Endoscope, Manisha Shrivastav, Elias Gounaris, Mohammad W. Khan, Jeffrey Ko, Stacy H. Ryu, Matthew Bogyo, Andrew Larson, Terrence A. Barrett, David J. Bentrem

Internal Medicine Faculty Publications

Purpose

The development of NIRF cathepsin activity probes offered the ability to visualize tumor associated tumor reaction and act as a surrogate marker to delineate the dysplastic lesions. One major type is a NIRF substrate of cathepsins (SBP), which is involved in catalytic way to produce high levels of fluorescence emission. The other major type (ABP) reacts with active cathepsins in stoichiometric manner since they bind covalently with their active center. Little is known about the sensitivity and the specificity of the NIRF probes to detect autochthonous developed dysplastic lesions. Dual laser NIRF endoscope provides a good tool to determine …

A Three-Dimensional Printed Low-Cost Anterior Shoulder Dislocation Model For Ultrasound-Guided Injection Training., Zachary Risler, Mark A. Magee, Jacob M. Mazza, Kelly Goodsell, Arthur K. Au, Resa E. Lewiss, Robert S. Pugliese, Bon Ku

Department of Emergency Medicine Faculty Papers

Anterior shoulder dislocations are the most common, large joint dislocations that present to the emergency department (ED). Numerous studies support the use of intraarticular local anesthetic injections for the safe, effective, and time-saving reduction of these dislocations. Simulation training is an alternative and effective method for training compared to bedside learning. There are no commercially available ultrasound-compatible shoulder dislocation models. We utilized a three-dimensional (3D) printer to print a model that allows the visualization of the ultrasound anatomy (sonoanatomy) of an anterior shoulder dislocation. We utilized an open-source file of a shoulder, available from embodi3D® (Bellevue, WA, US). After …

Designing Tailored Patient Education On Atrial Fibrillation, Tammy Toscos, R Ahmed, Romisa Rohani Ghahari, Elizabeth Martin, Shauna Wagner, Michelle Drouin, Michael J. Mirro

Presentations and Events

Background & Hypothesis: Research has revealed a high prevalence of depression, anxiety, and burnout among medical students accompanied by widespread lack of treatment. We hypothesize that by leveraging our study findings examining the use of telemental health(TMH) among youth (ages 14-24) alongside results from existing research focused on the mental health needs of medical students (median age at start 22-24 years old), we will gain valuable insight into the potential for TMH to address the needs of this high-risk population.

Methods: Using the Delphi method, a sample of 25 experts were surveyed anonymously, thus avoiding group pressure for conformity while …

Trunk Control And Gross Motor Outcomes After Body-Weight Supported Treadmill Training In Young Children With Severe Cerebral Palsy: A Case Series, Megan Flores, Carolyn Da Silva

Physical Therapy Collection

BACKGROUND AND PURPOSE: Children with cerebral palsy (CP) in Gross Motor Function Classification System (GMFCS) levels IV and V present with decreased gross motor function and trunk control that impacts their functional activities and participation in family activities. Research indicates body-weight supported treadmill training (BWSTT) may improve motor control for children with neuromotor disabilities. The toddler years present a window of opportunity for developmental changes. The purpose of this case series was to explore the impact of a 6-week BWSTT intervention on postural control and gross motor function in 3 young children with cerebral palsy in GMFCS levels IV and …

Caregiver Perspectives On Body-Weight Supported Treadmill Training As An Intervention For Young Children With Cerebral Palsy, Megan Flores, Carolyn Da Silva

Physical Therapy Collection

PURPOSE/HYPOTHESIS: Children with cerebral palsy (CP) in Gross Motor Function Classification System (GMFCS) levels IV and V present with challenges that impact their functional activities and participation in family activities. The purpose of this study was to examine caregivers’ perspectives on body-weight supported treadmill training (BWSTT) as an intervention for their young children with CP.

NUMBER OF SUBJECTS: Participants included 4 caregivers of children with CP in GMFCS levels IV (n = 2) and V (n = 2) who previously participated in 6 weeks of BWSTT.

MATERIALS/METHODS: Three children diagnosed with CP in GMFCS levels IV and V between the …

Mertk Is A Therapeutic Target In Combination With Radiation To Promote Adaptive Immune Tumor Responses, Garth Tormoen, Jason R Baird, Gwen Kramer, Shelly Bambina, Marka R Crittenden, Michael J. Gough

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Mertk is a member of the Tyro3-Axl-Mertk (TAM) family of receptors and regulates phagocytosis of dying cells by macrophages. Cancer cells killed by radiation therapy direct repolarization of macrophages into immune suppressive phenotypes. Mertk-/- mice grafted with immunogenic tumors have enhanced tumor control following ionizing radiation compared to Mertkwt mice. Gas6 is the endogenous ligand for Mertk and its ability to signal through Mertk requires a post-translational vitamin k-dependent modification that is inhibited by warfarin.

Methods: Mertk-/- and WT mice were injected subcutaneously in the flank with 5E4 CT26 cells (BALB/c) or 5E6 Panc02-SIY cells (C57BL/6) and allowed to …

Mv-626, A Potent And Selective Inhibitor Of Enpp1 Enhances Sting Activation And Augments T-Cell Mediated Anti-Tumor Activity In Vivo, Jason Baird, Gregory Dietsch, Vincent Florio, Michael Gallatin, Clayton Knox, Joshua Odingo, Marka Crittenden, Michael J. Gough

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: STING is an endogenous sensor of cGAMP, which is synthesized by cGAS following detection of cytoplasmic DNA. STING activation leads to interferon production and activation of inflammatory pathways that facilitate cytolytic T cell priming. STING agonists administered intratumorally show potent anti-tumor efficacy in a range of preclinical models; several agonists are in clinical development. Radiation therapy also increases cytoplasmic DNA levels in cancer cells, resulting in STING activation and secretion of inflammatory cytokines. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the phosphodiesterase that negatively regulates STING by hydrolyzing cGAMP. MV-626, a highly potent and selective ENPP1 inhibitor with 100% oral bioavailability …

Preliminary Evaluation Of A Novel Whole Slide Multispectral Assessment Of Seven Markers: Potential To Minimize Bias In The Characterization Of The Tumor Immune Environment, Carmen Ballesteros Merino, Shawn Jensen, Carla Coltharp, Kristin Roman, Chichung Wang, Nikhil Lonberg, Sebastian Marwitz, Tarsem Moudgil, William Miller, William Redmond, Yoshinobu Koguchi, Carlo Bifulco, Clifford Hoyt, Bernard A. Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: PD-L1 expression and tumor-mutational burden enrich for patients that respond to checkpoint blockade, but these evaluations are only a component of the entire story. Recently, our lab reported that evaluation of specific cell-cell relationships provided a powerful biomarker for overall survival in patients with HPV- head and neck cancer (HNSCC). However, the areas selected for analysis were operator selected “hot spots”. This approach introduces the potential for unconscious bias in the selection process. To address this, we have sought to perform whole slide evaluations of sections to compare with hot spot analysis. This study is a preliminary report applying …

Pegzilarginase In Combination With Agonist Anti-Ox40 Therapy Enhances T Cell Priming And Effector Function Leading To Improved Tumor Regression And Survival, Melissa Kasiewicz, Annah Rolig, Elizabeth Sturgill, Mark Badeaux, Scott Rowlinson, William L. Redmond

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Tumor cells defective in enzymes required for arginine biosynthesis are dependent upon arginine uptake from the environment. Extracellular depletion of arginine directly affects tumor cells, inducing autophagy and apoptosis. Pegzilarginase (AEB1102) is a bioengineered, pegylated, human arginase 1 (Aeglea Biotherapeutics) currently in phase I clinical trials. This arginine-depleting agent has been shown to both inhibit arginine auxotrophic tumor growth and to enhance the efficacy of PD-L1 blockade in preclinical models. In the current study, we investigated the therapeutic efficacy and mechanism of action of combined pegzilarginase/anti-OX40 (aOX40) immunotherapy. We hypothesized that pegzilarginase/aOX40 treatment would synergize to enhance T cell …

Integrative Spatially-Resolved, High-Plex Digital Profiling Enables Characterization Of Complex Immune Biology In The Tumor Microenvironment Of Mesothelioma, Carmen Ballesteros-Merino, Moritz Widmaier, Sarah Church, Thomas Herz, Alexei Budco, Das Medrikova, Ivan Kanchev, Andrew White, Douglas Hinerfeld, Shawn Jensen, John Handy, Rachel Sanborn, Carlo Bifulco, Sarah Warren, Joseph Beechem, Bernard .. Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Malignant mesothelioma is an aggressive cancer with poor prognosis and few effective therapies. Since mesothelioma is derived from the mesothelium of the lung, we hypothesize that immune cells in the tumor microenvironment (TME) may behave differently than other solid tumors. In our previous studies, utilizing multi-plexed immunofluorescence, we did not find immune phenotypes associated with improved patient survival. Here we describe a novel combination of two technologies to spatially characterize the interface between mesothelioma cells, stroma and immune cells in the TME in a high-plex capacity.

Methods: Ten FFPE mesothelioma tumors were characterized by Definiens’ Immune-Oncology Profiling (IOP) and …

Ethical Implications Of Treatment For Gender Dysphoria In Youth, Kelsey Hayes

Journal of Health Ethics

This manuscript explores ethical implications on treatment for youth with diagnosed gender dysphoria. The ethical considerations outlined and analyzed in this essay involve illuminating an understanding of whether the administration of pubertal suppression with GnRH agonists, and cross-sex hormones to children with gender dysphoria is morally justified as treatment to manage their psychological distress, or if safer more understood alternatives exist. This essay emphasizes that as health care professionals we must ensure youth with gender dysphoria receive adequate medical treatment and care however, this essay concludes through extensive literature review, that the use of inconclusive and under researched methods to …

Preliminary Results From A First-In-Human Phase 1 Study Of The Cd40 Agonist Monoclonal Antibody (Mab) Cdx-1140, Rachel Sanborn, Michael S. Gordon, Mark O'Hara, Nina Bhardwaj, Yi He, Tracey Rawls, Tibor Keler, Michael Yellin

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Agonist CD40 mAbs can mediate antitumor immunity through multiple mechanisms, including enhancing tumor antigen presentation, activation of tumoricidal macrophages, and direct growth inhibition/killing of CD40- expressing tumor cells. To fully exploit these mechanisms may require the mAb to be dosed at levels that provide significant tumor and tissue penetration, without dose-limiting-toxicities (DLT) from systemic CD40 activation. Our agonist CD40 mAb, CDX-1140, was selected based on its unique and linear dose-dependent in vitro and in vivo activity and is postulated will achieve maximum agonist activity at dose levels associated with good systemic exposure. CDX-1140 is a fully human IgG2 agonist …

Nktr-214 (Cd122-Biased Agonist) And Nktr-262 (Tlr7/8 Agonist) Combination Treatment Pairs Local Innate Immune Activation With Systemic Cd8+ T Cell Expansion To Enhance Anti-Tumor Immunity, Annah S. Rolig, Daniel Rose, Saul Kivimäe, Deborah Charych, Werner Rubas, Jonathan Zalevsky, William L. Redmond

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Radiation therapy (RT) remains the standard of care for many human cancers. Combining NKTR-214, a CD122-biased cytokine agonist conjugated with releasable polyethylene-glycol (PEG) chains, with local RT significantly enhanced therapeutic efficacy in preclinical models. Mechanistically, NKTR-214 provides sustained signaling through the IL-2 receptor pathway (IL-2Rβγ) to preferentially activate and expand effector CD8+ T and NK cells and RT modulates the tumor microenvironment (TME) to induce antigen-release. Together, NKTR-214/RT treatment resulted in improved therapeutic responses compared to either treatment alone. However, abscopal responses in murine tumors were modest, leading us to explore alternative approaches with the potential to elicit more …

Combined Anti-Pd-1 And Anti-Lag-3 Checkpoint Blockade Enhances Cd8+ Til Effector Function While Reducing Tregs Leading To Reduced Immune Suppression And Improved Overall Survival, Elizabeth Sturgill, Courtney Mick, David Jenkins, Johanna Kaufmann, William L. Redmond

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Checkpoint inhibition is a potent strategy to reinvigorate T cells. However, aCTLA-4 or aPD-1 monotherapy has not been effective for the majority of patients, resulting in the exploration of combinatorial approaches to improve treatment efficacy. One such target is LAG-3, which is upregulated on T cells that have experienced repeated antigen exposure, such as in the tumor microenvironment (TME), and is associated with reduced T cell effector function. In addition, high LAG-3 expression on regulatory T cells (Tregs) has been reported for patients with varying cancer types, providing an additional rationale for targeting LAG-3 with the aim of reducing …