Immunotherapy Commons^™

Temporal Trends In Outcomes In Patients With Adrenocortical Carcinoma: A Multidisciplinary Referral-Center Experience, Marilyne Daher, Jeena Varghese, Stephen K Gruschkus, Camilo Jimenez, Steven G Waguespack, Sara Bedrose, Lina Altameemi, Hadil Bazerbashi, Aung Naing, Vivek Subaiah, Matthew T Campbell, Amishi Y Shah, Miao Zhang, Rahul A Sheth, Jose A Karam, Christopher G Wood, Nancy D Perrier, Paul H Graham, Jeffery E Lee, Mouhammed Amir Habra

Faculty, Staff and Students Publications

CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies.

OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials.

METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019).

RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients …

Exploiting 4–1bb Immune Checkpoint To Enhance The Efficacy Of Oncolytic Virotherapy For Diffuse Intrinsic Pontine Gliomas, Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucía Marrodán, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martínez-Vélez, Iker Ausejo-Mauleon, Daniel De La Nava, Guillermo Herrador-Cañete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E De Andrea, María Villalba, Oren Becher, Massimo Squatrito, Verónica Matía, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed …

Notch-Induced Mdsc Recruitment After Ohsv Virotherapy In Cns Cancer Models Modulates Antitumor Immunotherapy, Yoshihiro Otani, Ji Young Yoo, Cole T Lewis, Samantha Chao, Jessica Swanner, Toshihiko Shimizu, Jin Muk Kang, Sara A Murphy, Kimberly Rivera-Caraballo, Bangxing Hong, Joseph C Glorioso, Hiroshi Nakashima, Sean E Lawler, Yeshavanth Banasavadi-Siddegowda, John D Heiss, Yuanqing Yan, Guangsheng Pei, Michael A Caligiuri, Zhongming Zhao, E Antonio Chiocca, Jianhua Yu, Balveen Kaur

Faculty, Staff and Student Publications

PURPOSE: Oncolytic herpes simplex virus-1 (oHSV) infection of brain tumors activates NOTCH, however the consequences of NOTCH on oHSV-induced immunotherapy is largely unknown. Here we evaluated the impact of NOTCH blockade on virus-induced immunotherapy.

EXPERIMENTAL DESIGN: RNA sequencing (RNA-seq), TCGA data analysis, flow cytometry, Luminex- and ELISA-based assays, brain tumor animal models, and serum analysis of patients with recurrent glioblastoma (GBM) treated with oHSV was used to evaluate the effect of NOTCH signaling on virus-induced immunotherapy.

RESULTS: TCGA data analysis of patients with grade IV glioma and oHSV treatment of experimental brain tumors in mice showed that NOTCH signaling significantly …

Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby

Research outputs 2022 to 2026

Medulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment of the disease and the impact of current therapies are limited. Preclinical models that recapitulate both the disease and immune environment are essential for understanding immune-tumor interactions and to aid the identification of new and effective immunotherapies. Using an immune-competent mouse model of aggressive Myc-driven medulloblastoma, we characterized the brain immune microenvironment and changes induced …

Combined Il-2, Agonistic Cd3 And 4–1bb Stimulation Preserve Clonotype Hierarchy In Propagated Non-Small Cell Lung Cancer Tumor-Infiltrating Lymphocytes, Parin Shah, Marie-Andrée Forget, Meredith L Frank, Peixin Jiang, Donastas Sakellariou-Thompson, Lorenzo Federico, Roohussaba Khairullah, Chantal Alexia Neutzler, Ignacio Wistuba, Chi-Wan B Chow, Yan Long, Junya Fujimoto, Shiaw-Yih Lin, Anirban Maitra, Marcelo V Negrao, Kyle Gregory Mitchell, Annikka Weissferdt, Ara A Vaporciyan, Tina Cascone, Jack A Roth, Jianjun Zhang, Boris Sepesi, Don L Gibbons, John V Heymach, Cara L Haymaker, Daniel J Mcgrail, Alexandre Reuben, Chantale Bernatchez

Faculty, Staff and Student Publications

Background: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method.

Methods: TIL from resected NSCLC tumors were initially cultured using (1) the traditional method using interleukin (IL)-2 alone in 24-well plates (TIL 1.0) or (2) IL-2 in combination with agonistic antibodies against CD3 and 4-1BB (Urelumab) in a G-Rex flask (TIL 3.0). TIL subsequently underwent a rapid expansion …

Corticosteroid-Refractory Myositis After Dual Braf And Mek Inhibition In A Patient With Braf V600e-Mutant Metastatic Intrahepatic Cholangiocarcinoma, Timothy P Diperi, Mehmet Demirhan, Daniel D Karp, Siqing Fu, David S Hong, Vivek Subbiah, Joann Lim, Leomar Y Ballester, Jean H Tayar, Maria E Suarez-Almazor, Milind Javle, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Intrahepatic cholangiocarcinoma is a rare malignancy, which is rich in actionable alterations. Genomic aberrations in the mitogen-activated protein kinase (MAPK) pathway are common, and

Allogeneic Transplant And Car-T Therapy After Autologous Transplant Failure In Dlbcl: A Noncomparative Cohort Analysis, Mehdi Hamadani, Ajay K Gopal, Marcelo Pasquini, Soyoung Kim, Xianmiao Qiu, Sairah Ahmed, Aleksandr Lazaryan, Vijaya Raj Bhatt, Andrew Daly, Premal Lulla, Stefan Ciurea, Jordan Gauthier, Vaibhav Agrawal, Natalie S Grover, Lazaros Lekakis, Dipenkumar Modi, Parastoo B Dahi, Megan M Herr, P Connor Johnson, Hamza Hashmi, Peiman Hematti, Frederick L Locke

Faculty, Staff and Students Publications

Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Faculty, Staff and Student Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Duncan NRI Faculty and Staff Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear Md, Phd

UROP Posters

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …

Neoadjuvant Checkpoint Inhibitor Immunotherapy For Resectable Mucosal Melanoma, Joel Ho, Jane Mattei, Michael Tetzlaff, Michelle D Williams, Michael A Davies, Adi Diab, Isabella C Glitza Oliva, Jennifer Mcquade, Sapna P Patel, Hussein Tawbi, Michael K Wong, Sarah B Fisher, Ehab Hanna, Emily Z Keung, Merrick Ross, Roi Weiser, Shirley Y Su, Michael Frumovitz, Larissa A Meyer, Amir Jazaeri, Curtis A Pettaway, B Ashleigh Guadagnolo, Andrew J Bishop, Devarati Mitra, Ahsan Farooqi, Roland Bassett, Silvana Faria, Priyadharsini Nagarajan, Rodabe N Amaria

Faculty, Staff and Student Publications

BACKGROUND: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.

METHOD: Under an institutionally approved protocol, we identified adult …

Epithelial Immunomodulation By Aerosolized Toll-Like Receptor Agonists Prevents Allergic Inflammation In Airway Mucosa In Mice, David L Goldblatt, Gabriella Valverde Ha, Shradha Wali, Vikram V Kulkarni, Michael K Longmire, Ana M Jaramillo, Rosha P Chittuluru, Adrienne Fouts, Margarita Martinez-Moczygemba, Jonathan T Lei, David P Huston, Michael J Tuvim, Burton F Dickey, Scott E Evans

Faculty, Staff and Student Publications

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells …

B Cells Are Required To Generate Optimal Anti-Melanoma Immunity In Response To Checkpoint Blockade, Shubhra Singh, Jason Roszik, Neeraj Saini, Vipul Kumar Singh, Karishma Bavisi, Zhiqiang Wang, Long T Vien, Zixi Yang, Suprateek Kundu, Richard E Davis, Laura Bover, Adi Diab, Sattva S Neelapu, Willem W Overwijk, Kunal Rai, Manisha Singh

Faculty, Staff and Student Publications

Immunotherapies such as checkpoint blockade therapies are known to enhance anti-melanoma CD8+ T cell immunity, but only a fraction of patients treated with these therapies achieve durable immune response and disease control. It may be that CD8+ T cells need help from other immune cells to generate effective and long-lasting anti-tumor immunity or that CD8+ T cells alone are insufficient for complete tumor regression and cure. Melanoma contains significant numbers of B cells; however, the role of B cells in anti-melanoma immunity is controversial. In this study, B16 melanoma mouse models were used to determine the role of B cells …

The Effects Of Glucocorticoids And Immunosuppressants On Cancer Outcomes In Checkpoint Inhibitor Therapy, Sebastian Bruera, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

The emergence of checkpoint inhibitors has created a paradigm shift for the treatment of various malignancies. However, although these therapies are associated with improved survival rates, they also carry the risk of immune-related adverse events (irAEs). Moderate to severe irAEs are typically treated with glucocorticoids, sometimes with the addition of immunosuppressants as steroid-sparing therapy. However, it is unclear how glucocorticoids and immunosuppressants may impact cancer survival and the efficacy of immune checkpoint therapy on cancer. In this narrative review, we discuss the effects of glucocorticoids and immunosuppressants including methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, tumor-necrosis factor (TNF)-inhibitors, interleukin-6 inhibitors, interleukin-1 inhibitors, …

Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner

Faculty, Staff and Students Publications

In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with …

Reduced Pro-Inflammatory Dendritic Cell Phenotypes Are A Potential Indicator Of Successful Peanut Oral Immunotherapy, Sara Anvari, Levi B Watkin, Charles G Minard, Kimberly Schuster, Oluwatomi Hassan, Aikaterini Anagnostou, Jordan S Orange, David B Corry, Carla M Davis

Faculty, Staff and Students Publications

Dendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). Delineation of early immunologic changes contributing to desensitization would help clarify the POIT mechanism of action. We analyzed dendritic cells in 15 pediatric subjects (5-12 years) undergoing a phase 1 single-center POIT study. We examined dendritic cells at baseline, 6-, 12-, 18- and 24-weeks after initiation of POIT and responders of therapy were compared to non-responders and healthy controls. …

Posttranslational Modifications In Pd-L1 Turnover And Function: From Cradle To Grave, Xinfang Yu, Wei Li, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is one of the most classic immune checkpoint molecules. Cancer cells express PD-L1 to inhibit the activity of effector T cells' cytotoxicity through programmed death 1 (PD-1) engagement in exposure to inflammatory cytokines. PD-L1 expression levels on cancer cells might affect the clinical response to anti-PD-1/PD-L1 therapies. Hence, understanding molecular mechanisms for regulating PD-L1 expression is essential for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade. Posttranslational modifications (PTMs), including phosphorylation, glycosylation, ubiquitination, and acetylation, regulate PD-L1 stability, cellular translocation, and interaction with its receptor. A coordinated positive and negative regulation via PTMs is …

An Investigation Of Healthcare Supports For Those With Food Allergy In Ireland, Joseph Bolger, Nicola Blake, Sneha Vinod

International Undergraduate Journal of Health Sciences

Introduction: In Ireland, around 5% of children and 3% adults have food allergy (134,000 people). This current paper describes a survey that was carried out on a subset of service-users with the aim of identifying whether there is a need for increased specialist medical services and/or for a funded charity such as Anaphylaxis Ireland, defunct since 2015.

Materials & Methods: These needs were assessed via an online survey using Google Forms. The survey was conducted from 17-27th February 2020. There were 31 questions in total, relating to topics such as symptoms, clinical wait times, satisfaction with care provided and demand …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, Iujhs Full Issue

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

The Immune Microenvironment And Relation To Outcome In Patients With Advanced Breast Cancer Treated With Docetaxel With Or Without Gemcitabine, Elisabeth S. Stovgaard, Karama Asleh, Nazia Riaz, Samuel Leung, Dongxia Gao, Lise B. Nielsen, Anne-Vibeke Lænkholm, Eva Balslev, Maj-Britt Jensen, Dorte Nielsen, Torsten O. Nielsen

Centre for Regenerative Medicine & Stem Cell Research

Preclinical studies suggest that some effects of conventional chemotherapy, and in particular, gemcitabine, are mediated through enhanced antitumor immune responses. The objective of this study was to use material from a randomized clinical trial to evaluate whether patients with preexisting immune infiltrates responded better to treatment with gemcitabine + docetaxel (GD) compared to docetaxel alone. Formalin fixed, paraffin-embedded breast cancer tissues from SBG0102 phase 3 trial patients randomly assigned to treatment with GD or docetaxel were used. Immunohistochemical staining for CD8, FOXP3, LAG3, PD-1, PD-L1 and CD163 was performed. Tumor infiltrating lymphocytes (TILs) and tumor associated macrophages were evaluated. Prespecified …

Harnessing The Power Of Trained Immunity In The Setting Of Pancreatic Cancer: A Novel Mechanism Of Immune Trafficking And Tumor Control., Anne Elena Geller

Electronic Theses and Dissertations

Despite the success of immunotherapy in many types of cancer, pancreatic adenocarcinoma (PDAC) has yet to benefit. Innate immune cells are critical to antitumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Though trained innate immunity has mostly been investigated in the context of infection, the induction of trained innate immunity could also protect against tumors, and specifically pancreatic tumors. Here, we demonstrate that yeast-derived particulate β-glucan, a known inducer of trained immunity, traffics to the pancreas following IP administration. This causes …

Cxcl11 And Smica As Predictive Biomarkers For Efficacy Of Anti-Ctla4 Immunotherapy, Keith Sadoon Bahjat, Helena Maria Hoen, Yoshinobu Koguchi, Alan J. Korman

Technology Transfer - Patents

Provided herein are methods for selecting a cancer patient for anti-CTLA-4 immunotherapy, or predicting whether a cancer patient will respond to anti-CTLA4 immunotherapy, based on measured levels of CXCL1 1 and/or sMICA. Such methods are useful for determining whether an anti-CTLA-4 immunotherapy is likely to improve overall survival of a cancer patient. Also provided herein are methods of treating a cancer patient with an anti-CTLA-4 immunotherapy, wherein the patient is first tested for levels of CXCL1 1 and/or sMICA. Also provided are methods for treating a cancer patient with a CXCL1 1 antagonist or sMICA ant agonist alone, or in …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Immune Checkpoint Inhibitor Therapy In Hiv-Associated Merkel Cell Carcinoma: A Case Series Of 3 Patients., Song Y Park, Candice Church, Nora A Alexander, Michi M Shinohara, Kelly G Paulson, Karl D Lewis, Nancy S Lee, Paul Nghiem

Articles, Abstracts, and Reports

No abstract provided.

The Intellectual Property Of Covid-19, Ana Santos Rutschman

All Faculty Scholarship

The response to COVID-19 is indissolubly tied to intellectual property. In an increasingly globalized world in which infectious disease pathogens travel faster and wider than before, the development of vaccines, treatments and other forms of medical technology has become an integral part of public health preparedness and response frameworks. The development of these technologies, and to a certain extent the allocation and distribution of resulting outputs, is informed by intellectual property regimes. These regimes influence the commitment of R&D resources, shape scientific collaborations and, in some cases, may condition the widespread availability of emerging technologies. As seen throughout this chapter, …

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume I-Conceptual Challenges., Sergio Rutella, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Alessandra Cesano

Articles, Abstracts, and Reports

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial …

Efficacy And Safety Of First-Line Avelumab In Patients With Advanced Non-Small Cell Lung Cancer: Results From A Phase Ib Cohort Of The Javelin Solid Tumor Study., Claire F Verschraegen, Guy Jerusalem, Edward F Mcclay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew H Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley

Articles, Abstracts, and Reports

INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 156 patients were enrolled …

Neoantigen-Specific Cd4(+) T-Cell Response Is Critical For The Therapeutic Efficacy Of Cryo-Thermal Therapy, Peng Peng, Hong-Ming Hu, Ping Liu, Lisa X Xu

Articles, Abstracts, and Reports

Background: Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.

Methods: The long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …