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Full-Text Articles in Medicine and Health Sciences

Sociocultural And Socioeconomic Determinants Of Organ Donation, Amy Gagliano Jul 2020

Sociocultural And Socioeconomic Determinants Of Organ Donation, Amy Gagliano

Posters@Research Events

Recent research has indicated that community-level characteristics are predictive of donor designation in a given region. This current study extends the body of this work to consider the potential impact of regional level sociocultural and socioeconomic determinants of health on measures of Organ Procurement Organizations’ (OPOs) success at facilitating organ transplants. Using select indicators from The National County Health Rankings dataset, county-level indicators were aggregated to provide estimates of health within each of the 57 national OPOs donation areas. Significant associations were documented.


Reducing Benzodiazepine Use For The Treatment Of Insomnia And Supporting Nonpharmacological Therapies, Unchan Pyon Jan 2019

Reducing Benzodiazepine Use For The Treatment Of Insomnia And Supporting Nonpharmacological Therapies, Unchan Pyon

Family Medicine Clerkship Student Projects

Most medical organizations recommend against the use of benzodiazepine use for the treatment of insomnia, especially in the elderly. However, the percentage of the adult population on benzos increase with age: 7.5% in adults ages 51-64; 9% in adults over 65. Alternative therapies for insomnia, including online CBT, require more commitment than taking a medication so many patients opt for medication. This project aims to increase awareness of benzodiazepine use for insomnia and provide support for nonpharmacological therapies.


Updated Efficacy Of First Or Second-Line Pembrolizumab Plus In Metastatic Triple Negative Breast Cancer And Correlations With Baseline Lymphocyte And Naïve Cd4+ T-Cell Count, David Page, Joanna Pucilowska, Laura Bennetts, I Kim, Katherine Sanchez, Maritza Martel, Alison Conlin, Nikki Moxon, Staci Mellinger, Anupama Acheson, K Kemmer, Z Mitri, J Vuky, J Ahn, C Abaya, T Manigault, R Basho, Walter Urba, Hl Mcarthur Dec 2018

Updated Efficacy Of First Or Second-Line Pembrolizumab Plus In Metastatic Triple Negative Breast Cancer And Correlations With Baseline Lymphocyte And Naïve Cd4+ T-Cell Count, David Page, Joanna Pucilowska, Laura Bennetts, I Kim, Katherine Sanchez, Maritza Martel, Alison Conlin, Nikki Moxon, Staci Mellinger, Anupama Acheson, K Kemmer, Z Mitri, J Vuky, J Ahn, C Abaya, T Manigault, R Basho, Walter Urba, Hl Mcarthur

Other Publications

Background: In mTNBC, anti-PD-1/L1 monotherapy is most effective when administered early in the course of disease, with recent trials demonstrating overall response rates (ORR) of 23-26% in the first-line setting and 5-6% in later lines. This may reflect iatrogenic lymphopenia from preceding cytotoxic chemotherapy. Furthermore, curative-intent chemotherapy is associated with prolonged suppression of naïve CD4+ cells, a T-cell subset that may play a critical role in the generation of de novo anti-tumor immune responses. We present the final clinical results of a pilot study evaluating the safety and efficacy of combining pembrolizumab plus standard-of-care capecitabine in the first/second-line ...


Perilymphatic Irx-2 Cytokine Therapy To Enhance Tumor Infiltrating Lymphocytes And Pd-L1 Expression Preceding Curative-Intent Therapy In Early Stage Breast Cancer, Joanna Pucilowska, Venkatesh Rajamanickam, Katherine Sanchez, Valerie Conrad, Alison Conlin, Shagheyegh Aliabadi-Wahle, Shu-Ching Chang, Gary Grunkemeier, Nikki Moxon, Staci Mellinger, Maritza Martel, James Egan, Monil Shah, David B Page Dec 2018

Perilymphatic Irx-2 Cytokine Therapy To Enhance Tumor Infiltrating Lymphocytes And Pd-L1 Expression Preceding Curative-Intent Therapy In Early Stage Breast Cancer, Joanna Pucilowska, Venkatesh Rajamanickam, Katherine Sanchez, Valerie Conrad, Alison Conlin, Shagheyegh Aliabadi-Wahle, Shu-Ching Chang, Gary Grunkemeier, Nikki Moxon, Staci Mellinger, Maritza Martel, James Egan, Monil Shah, David B Page

Other Publications

Background: Cytokines are being explored as a therapeutic strategy to modulate the tumor microenvironment and facilitate immunotherapy benefit in breast cancer. Here, we investigate a locoregional therapeutic approach whereby cytokines (IRX-2) are administered into the subcutaneous peri-areolar tissue (in an anatomic distribution similar to sentinel lymph node mapping) to facilitate immune cell recruitment/activation within the draining lymph nodes and tumor in ESBC. IRX-2 is derived from ex vivo phytohemagglutinin-stimulated lymphocytes and contains multiple cytokines including IL-1β, IL-2, TNF-α, IFN-γ, IL-6, IL-8, and GM-CSF, with stable concentrations from lot to lot. Preclinically, IRX-2 activates T-cells and natural killer (NK) cells ...


December 2018, Swosu Bulldog Wellness Committee Dec 2018

December 2018, Swosu Bulldog Wellness Committee

SWOSU BULLDOG WELLNESS

Money savers for Holiday Shoppers

We hate to be negative this time of year, but gift-giving can get expensive! How to pay for all those gifts? Here are a few suggestions…

Healthy Holiday Habits

Travel, parties, big meals and snack foods at the office all create a challenging environment for eating healthy. Add in several days of travel with little scheduled physical activity, and it becomes a real effort to stay on track. Here are some helpful hints to help keep your holidays healthy!


A 6 Week Balance And Gait Training Program Using The Alterg For A Patient With Cervical Myelopathy After Spinal Decompression Surgery: A Case Report, Palak Patel Dec 2018

A 6 Week Balance And Gait Training Program Using The Alterg For A Patient With Cervical Myelopathy After Spinal Decompression Surgery: A Case Report, Palak Patel

Case Report Posters

Spinal stenosis is the narrowing of the spinal canal which can cause radiculopathy or myelopathy symptoms due to compression of the spinal cord. About 80% of patients of 70 years old have some level of stenosis. There is limited research on prognosis for patients with cervical myelopathy and subsequent spinal decompression surgery. AlterG treadmill (AlterG Anti-Gravity Treadmill M320/F320, Fremont, CA) is an antigravity treadmill that is considered a body weight support system used in progressive gait retraining. The purpose of this case report is to assess the effectiveness of balance and gait training on the AlterG in a geriatric ...


Gait Training A Patient Who Was Deaf With Multiple Total Hip Revisions: A Case Report, Natalie Slattery, Kirsten Buchanan Dec 2018

Gait Training A Patient Who Was Deaf With Multiple Total Hip Revisions: A Case Report, Natalie Slattery, Kirsten Buchanan

Case Report Posters

93% of patients who have a total hip arthroplasty (THA) are due to end-stage osteoarthritis. 15-30% of patients who survive a stroke continue to live with a long-term disability. The most common abnormal gait pattern after surviving a stroke is due to hemiparesis. Patients who are deaf require greater visual and tactile cueing during gait training. Gait training has been shown to normalize gait patterns and increase functional mobility in patients after a total hip replacement (THR), THA revision and/or stroke. There is a lack of research investigating the optimal gait training plan of care (POC) for a patient ...


Comprehensive Physical Therapy Management Of A Patient With Decreased Shoulder Function And A History Of Breast, Lung, And Oral Cancer: A Case Report, Andrew Chongaway, Amy J. Litterini Dec 2018

Comprehensive Physical Therapy Management Of A Patient With Decreased Shoulder Function And A History Of Breast, Lung, And Oral Cancer: A Case Report, Andrew Chongaway, Amy J. Litterini

Case Report Posters

Multiple primary cancers are uncommon in the same individual with an incidence rate of 2-17%. Surgery, chemotherapy, endocrine therapy, and Surgery, chemotherapy, endocrine therapy, and radiation may result in immediate and/or long radiation may result in immediate and/or long-term effects on the musculoskeletal, cardiopulmonary, nervous, and integumentary systems potentially resulting in decreased functional mobility and quality of life (QOL) for the individual. The purpose of this case report was to describe a comprehensive physical therapy (PT) plan using manual therapy and therapeutic exercises in the management of decreased shoulder function for a patient with a history of breast ...


Restoring Functional Mobility In An Adult Patient Secondary To Subtrochanteric Femur Fracture Surgical Repair: A Case Report, Brittany Gray Dec 2018

Restoring Functional Mobility In An Adult Patient Secondary To Subtrochanteric Femur Fracture Surgical Repair: A Case Report, Brittany Gray

Case Report Posters

The National Highway Traffic Safety Administration noted 7,277,000 police reported motor vehicle accidents (MVA) in the United States in 2016.1 As a result, 2,177,000 people were injured. In 2008, approximately 340,000 emergency department visits were because of hip fractures. Femur fractures average $40,000 in medical bills in the first year following injury and another $5,000 in succeeding years. A review of 12 trials resulted in mixed evidence on the necessity of skilled physical therapy (PT) interventions to maximize functional mobility in individuals with femur fractures. The purpose of this case report was ...


Balance And Strength Interventions For An Older Individual With Peripheral Polyneuropathy: A Case Report, Hanna Geib Dec 2018

Balance And Strength Interventions For An Older Individual With Peripheral Polyneuropathy: A Case Report, Hanna Geib

Case Report Posters

Peripheral polyneuropathy (PPN) is a condition resulting from damage to the peripheral nervous system. PPN occurs in a distal and symmetrical pattern, often affecting the toes and the soles of the feet. Numbness, tingling, paresthesias, or burning are common symptoms of PPN. 20-25% of cases are idiopathic. Can affect functional mobility due to proprioceptive sensory losses and general weakness of extensor muscles, which then results in unsteadiness of gait and impaired balance. Treatment can consist of pharmacological and physical therapy interventions in order to manage symptoms. Recent literature demonstrated that following participation in a strength and balance training program, individuals ...


Inpatient Physical Therapy Management For A Patient With Chronic Pulmonary Complications Secondary To Multiple Lobectomies: A Case Report, Bayley Archinal Dec 2018

Inpatient Physical Therapy Management For A Patient With Chronic Pulmonary Complications Secondary To Multiple Lobectomies: A Case Report, Bayley Archinal

Case Report Posters

Bronchiectasis is a disease defined by abnormal dilation of the bronchi, which is a result of recurrent infections and/or chronic inflammation. A lobectomy is the surgical removal of one lobe of a lung and reduces the symptoms of bronchiectasis. Patients who undergo this surgery are more likely to have long-term pulmonary limitations. There is little to no literature regarding the long term treatment of patients who underwent multiple lobectomies. The purpose of this case report was to describe an appropriate intervention program for an 82-year-old female who suffered from multiple pulmonary complications secondary to multiple lobectomies.


The Scoop, Vol. 5 Issue 9, December 2018, Health Sciences Library Dec 2018

The Scoop, Vol. 5 Issue 9, December 2018, Health Sciences Library

Volume 5

Latest news and events from the Health Sciences Library in our monthly newsletter for December 2018.


An Academia-Industry Partnership For Planning And Executing A Community-Based Feeding Study, Cara B. Ebbeling, Gloria L. Klein, Julia M W Wong, Lisa Bielek, Patricia K. Louto, David S. Ludwig, Ralph G. Eddy, Lauren Stone, Paul R. Lakin, Megan Sandman, Courtenay Devlin, Linda Seger-Shippee, Dina Wiroll Nov 2018

An Academia-Industry Partnership For Planning And Executing A Community-Based Feeding Study, Cara B. Ebbeling, Gloria L. Klein, Julia M W Wong, Lisa Bielek, Patricia K. Louto, David S. Ludwig, Ralph G. Eddy, Lauren Stone, Paul R. Lakin, Megan Sandman, Courtenay Devlin, Linda Seger-Shippee, Dina Wiroll

(FS)2 Scholarly Publications

A research team from Boston Children’s Hospital and Harvard Medical School conducted a community-based feeding study in collaboration with Framingham State University (FSU) and Sodexo, the food service contractor at FSU. The study was a randomized controlled trial, implemented on the FSU campus. For the final year of the study, a satellite feeding site was established at Assabet Valley Regional Technical High School. The purpose of the study was to assess the biological effects of different macronutrient diets. An academia-industry partnership was developed to overcome common challenges associated with hospital-based feeding studies. Benefits included the following: a study site ...


Effects Of A Low Carbohydrate Diet On Energy Expenditure During Weight Loss Maintenance: Randomized Trial, Cara B. Ebbeling, Henry A. Feldman, Gloria L. Klein, Julia M.W. Wong, Lisa Bielek Bielek, Sarah K. Steltz, Patricia K. Louto, Robert R. Wolfe, William W. Wong, David S. Ludwig Nov 2018

Effects Of A Low Carbohydrate Diet On Energy Expenditure During Weight Loss Maintenance: Randomized Trial, Cara B. Ebbeling, Henry A. Feldman, Gloria L. Klein, Julia M.W. Wong, Lisa Bielek Bielek, Sarah K. Steltz, Patricia K. Louto, Robert R. Wolfe, William W. Wong, David S. Ludwig

(FS)2 Scholarly Publications

From the abstract "OBJECTIVE To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure. DESIGN Randomized trial. SETTING Multicenter collaboration at US two sites, August 2014 to May 2017. PARTICIPANTS 164 adults aged 18-65 years with a body mass index of 25 or more. INTERVENTIONS After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy ...


The Scoop, Vol. 5 Issue 8, November 2018, Health Sciences Library Nov 2018

The Scoop, Vol. 5 Issue 8, November 2018, Health Sciences Library

Volume 5

Latest news and events from the Health Sciences Library in our monthly newsletter for November 2018.


November 2018, Swosu Bulldog Wellness Committee Nov 2018

November 2018, Swosu Bulldog Wellness Committee

SWOSU BULLDOG WELLNESS

Healthier Dishes to Serve This Thanksgiving

This year, why not make Thanksgiving not only delicious but also a health-boosting experience that’s truer to the origins of the holiday? For most of us, our traditional Thanksgiving meal has shifted away from the natural foods enjoyed by the 17th-century celebrants. But it’s not that difficult to get back to preparing delicious food that is fresh from the harvest…and packed with nutrition.


The Santa Clara, 2018-11-01, Santa Clara University Nov 2018

The Santa Clara, 2018-11-01, Santa Clara University

The Santa Clara

No abstract provided.


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 Nov 2018

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 ...


Single Cell Sequencing To Identify Tcrs That Recognize Autologous Tumor Cells After Vaccination With Allogeinic Dribble Vaccine, Hong-Ming Hu, Christopher C. Paustian, Zhifa Wen, Tarsem L. Moudgil, Traci L. Hilton, Sam Bookhardt, Guangjie Yu, Eric Tran, Venkatesh Rajamanickam, Walter Urba, Rachel E. Sanborn, Bernard A. Fox Nov 2018

Single Cell Sequencing To Identify Tcrs That Recognize Autologous Tumor Cells After Vaccination With Allogeinic Dribble Vaccine, Hong-Ming Hu, Christopher C. Paustian, Zhifa Wen, Tarsem L. Moudgil, Traci L. Hilton, Sam Bookhardt, Guangjie Yu, Eric Tran, Venkatesh Rajamanickam, Walter Urba, Rachel E. Sanborn, Bernard A. Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Adoptive immunotherapy with tumor-specific TCR gene-modified T cells has the potential to eradicate bulky disease. Traditional methods of TCR identification require lengthy in vitro culture to generate clonal T-cell populations, which adds time and complexity to this promising therapy. Here we described a simplified and reliable method to identify TCRs by single cell TCR sequencing of cells sorted with antibodies against T-cell surface markers that are up-regulated only when they are stimulated with specific tumor cell antigens.

Methods: A tumor-infiltrating lymphocyte (TIL) culture with T cells reactive against autologous tumor was generated from a brain metastasis of a patients ...


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 Nov 2018

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 ...


Assessment Of Consistency Of Multiplex Fluorescent Immunohistochemistry Data Across Multiple Users Utilizing Different Quantitative Analysis Strategies, Shawn Jensen, Carmen Ballesteros-Merino, Sebastian Marwitz, Nikhil Lonberg, Bernard A Fox Nov 2018

Assessment Of Consistency Of Multiplex Fluorescent Immunohistochemistry Data Across Multiple Users Utilizing Different Quantitative Analysis Strategies, Shawn Jensen, Carmen Ballesteros-Merino, Sebastian Marwitz, Nikhil Lonberg, Bernard A Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Tools that facilitate examination of the tumor microenvironment in cancer patients who either respond or do not respond to treatment are informative to the future design of immunotherapeutic strategies. Multiplex fluorescent immunohistochemistry (mIHC) is a technique enabling examination of the number and location of cells within the tumor microenvironment. Recently, we described the Cumulative Suppression Index (CSI), which examines the number of CD8+ T cells in the invasive margin of tumor combined with the number of FoxP3+ or PD-L1+ cells within 30 um of CD8+ T cells[1]. This CSI correlated with overall survival in a cohort of 119 ...


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 Nov 2018

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 ...


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 Nov 2018

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 ...


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 Nov 2018

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 ...


Delayed Immune-Related Events After Discontinuation Of Immunotherapy – Dire Syndrome?, Marcus Couey, R. Bryan Bell, Ashish Patel, Marka R Crittenden, Brendan Curti, Rom Leidner Nov 2018

Delayed Immune-Related Events After Discontinuation Of Immunotherapy – Dire Syndrome?, Marcus Couey, R. Bryan Bell, Ashish Patel, Marka R Crittenden, Brendan Curti, Rom Leidner

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Although the temporality of immune-related adverse events (irAE) is well-recognized during immunotherapy to be highly variable and often delayed,[1] post-immunotherapy irAE are rarely described and potentially under-recognized. In 2013, two cases were reported in abstract form in Deutschen Dermatologischen Gesellschaft.[2] In July 2018 a case of autoimmune hepatitis eight months post-immunotherapy was reported in The Oncologist[3] and a dermatologic series appeared online in JAMA Dermatology.[4] With expanding indications for IO and an increasing number of clinical trials in the curative-neoadjuvant setting, larger numbers of patients are being treated in earlier stages of disease and often ...


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 Nov 2018

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 ...


Application Of Multiplexed Immunofluorescence And Multispectral Imaging To Investigate Tgfβ Pathway Activation Of Immune Cell Populations In Human Lung Cancer, Sebastian Marwitz, Carmen Ballesteros-Merino, Shawn Jensen, Bernard A Fox Nov 2018

Application Of Multiplexed Immunofluorescence And Multispectral Imaging To Investigate Tgfβ Pathway Activation Of Immune Cell Populations In Human Lung Cancer, Sebastian Marwitz, Carmen Ballesteros-Merino, Shawn Jensen, Bernard A Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer-related death worldwide and is usually diagnosed in an already locally or systemically advanced state. Depending on the stage of the tumor, surgical therapy is limited and systemic therapy required. Recent developments with targeted therapies and immune checkpoint blockade resulted in improved survival for a limited number of patients but the magnitude of patients will still progress. The transforming growth factor beta signaling pathway (TGFβ) is frequently activated in lung cancer, involved in malignant progression and a possible target for therapy [1]. TGFβ signaling is known to inhibit immune ...


Inducible T Cell Co-Stimulator (Icos) Is Upregulated On Lymphocytes Following Radiation Of Tumors And Icos Agonism In Combination With Radiation Results In Enhanced Tumor Control, Michael J. Gough, Shelly Bambina, Monica Gostissa, Christopher Harvey, David Friedman, Marka R Crittenden Nov 2018

Inducible T Cell Co-Stimulator (Icos) Is Upregulated On Lymphocytes Following Radiation Of Tumors And Icos Agonism In Combination With Radiation Results In Enhanced Tumor Control, Michael J. Gough, Shelly Bambina, Monica Gostissa, Christopher Harvey, David Friedman, Marka R Crittenden

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Radiation and co-stimulatory ligands or checkpoint inhibitors have demonstrated improved anti-tumor immunity and overall survival in preclinical animal studies. However, the results of human trials suggest we have not yet found the optimal combination. Here we demonstrate upregulation of ICOS expression on T cells following focal tumor radiation and test the hypothesis that ICOS agonism in combination with radiation will enhance the immunologic effect of radiation resulting in increased survival.

Methods: BALB/c mice bearing CT26 tumors or C57BL/6 mice bearing Panc02 tumors were treated at d14 with 20Gy CT guided radiation therapy and anti-ICOS antibody or isotype ...


Open-Source Digital Image Analysis Of Whole-Slide Multiplex Immunohistochemistry, Nikhil Lonberg, Carmen Ballesteros-Merino, Shawn Jensen, Bernard A Fox Nov 2018

Open-Source Digital Image Analysis Of Whole-Slide Multiplex Immunohistochemistry, Nikhil Lonberg, Carmen Ballesteros-Merino, Shawn Jensen, Bernard A Fox

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: Successful digital image analysis (DIA) of cancer tissue is accurate and reproducible. These points of emphasis have brought procedures like the tissue microarray (TMA) and hotspot regions of interest (ROI) under scrutiny. The nature in which a pathologist selects TMAs and ROIs is conducive to bias. Whole Slide Imaging (WSI) offers a solution in its unbiased region selection and consideration of a larger tissue sample. However, options for softwares that can handle such large throughput are scarce. Additionally, while multiplex immunohistochemistry (mIHC) is becoming popular [1], documentation of its digital analysis tools remains minimal [2]. The combination of these ...


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 Nov 2018

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 ...