Immunotherapy Commons^™

Mathematical Modeling Of The Car T-Cell Therapy, Emek Kose, Elizabeth Zollinger, Samantha Elliott

Biology and Medicine Through Mathematics Conference

No abstract provided.

Exosomal Communication By Metastatic Osteosarcoma Cells Modulates Alveolar Macrophages To An M2 Tumor-Promoting Phenotype And Inhibits Tumoricidal Functions, Kerri Wolf

Dissertations and Theses (Open Access)

Osteosarcoma metastasizes to the lung, and there is a link between the predominance of tumor promoting immunosuppressive M2 macrophages in the metastases and poor patient survival. By contrast, M1macrophage predominance correlates with longer survival. M2 macrophages can be induced by various stimuli in the tumor microenvironment, including exosomes, which are 40- to 150-nm vesicles that are involved in intercellular communication and contribute to tumor progression and immune evasion. Recognizing that tumor cells can influence the tumor microenvironment to make it more permissive and because of the link between M2 dominance and curtailed patient survival, we evaluated the effect of …

Loss Of Caspase-8 Function In Combination With Smac Mimetic Treatment Sensitizes Head And Neck Squamous Carcinoma To Radiation Through Induction Of Necroptosis., Burak Uzunparmak

Dissertations and Theses (Open Access)

Caspase-8 (CASP8) is one of the most frequently mutated genes in Head and Neck Squamous Carcinomas (HNSCC), and mutations of CASP8 are associated with poor overall survival. The distribution of these mutations in HNSCC suggests that they are likely to be inactivating. Inhibition of CASP8 has been reported to sensitize cancer cells to necroptosis, a unique cell death mechanism. Here, we evaluated how CASP8 regulates necroptosis in HSNCC using cell line models and syngeneic mouse xenografts. In vitro, knockdown of CASP8 rendered HNSCCs susceptible to necroptosis induced by a second mitochondria-derived activator of caspase (SMAC) mimetic, Birinapant, when combined …

Mast Cells As Novel Effector Cells In The Pathogenesis Of Chronic Graft-Versus-Host Disease, Ethan Strattan

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host-disease (GVHD), a condition wherein the donor cells recognize the patient tissues as non-self. GVHD can manifest anywhere from weeks to decades post-transplant and is classified as either acute or chronic GVHD, both of which are significant causes of transplant-related morbidity and mortality.

However, GVHD is a complex, multifactorial, and enigmatic disease. The factors driving GVHD at the cellular and molecular level are incompletely understood. Immunosuppression targeting T-cells has …

Immunotherapy: Therapy Vs. Enhancement, Mariah Daly

Honors Program Theses

The battle against cancer is a long-standing struggle that has resulted in new information and the development of novel medical technologies. Current research aims to figure out a way to reprogram cells and bodily mechanisms to eliminate those cells that are cancerous without destroying healthy cells in the process. Methods which use the body’s own mechanisms, such as immunotherapy, have shown and continue to show potential for specifically targeting cancer cells. Adoptive T cell therapy is one form of immunotherapy that has gained significant attention and focus in the field. Therapies improve conditions up to the normal state of being, …

Identification Of Imiquimod As A Potential Combination For Anti-Cd47 Antibodies In Cancer Therapy, Nicole Brittaney Pang

Scripps Senior Theses

The avenues of targeted immunotherapy offers a promise of less toxic treatment options for those battling different forms of cancer. Specifically, the process of hijacking a patient’s own immune system to fight cancer from within versus using external treatments like chemotherapy which is extremely damaging to the patient. One such avenue includes the usage of monoclonal antibodies as an effective modality for immunotherapy. Cluster of Differentiation 47 (CD47), also known as the ‘don’t eat me signal’, aids in cell proliferation and evasion of phagocytosis and has been found to be a target for stopping tumorigenesis. Previous research has been successful …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Enhancing Chemosensitivity Of Lung Cancers By Manipulating The Tumor Microenvironment: Local Lung Delivery And Nanocarrier-Based Therapies, Hanming Zhang

Theses and Dissertations

Cancer is the second leading cause of death in United States causing an estimated six hundred thousand death in 2019. Among different types of cancer, lung cancer is the leading cause of cancer related death in both male and female. While targeted therapy and immunotherapy have shown promising clinical outcomes, currently there remain a significant proportion of patients who do not benefit from these strategies or who cannot tolerate them, making Pt based doublet chemotherapy still an indispensable component in almost all stages of treatment. However, partially due to the poor tumor distribution of small molecule drug, the development of …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Comments On The Preliminary Framework For Equitable Allocation Of Covid-19 Vaccine, Ana Santos Rutschman, Julia Barnes-Weise, Robert Gatter, Timothy L. Wiemken

All Faculty Scholarship

On September 1, 2020 the National Academies released a draft framework for Equitable Allocation of a COVID-19 Vaccine. In this response, we analyze the proposed framework and highlight several areas.

Among the proposed changes, we highlight the need for the following interventions. The final framework for distribution of COVID-19 vaccines should give a higher priority to populations made most vulnerable by the social determinants of health. It should incorporate more geography-based approaches in at least some of the four proposed phases of vaccine distribution. It should address the possibility of a vaccine being made available through an emergency use authorization …

Eftilagimod Alpha, A Soluble Lymphocyte Activation Gene-3 (Lag-3) Protein Plus Pembrolizumab In Patients With Metastatic Melanoma, Victoria Atkinson, Adnan Khattak, Andrew Haydon, Melissa Eastgate, Amitesh Roy, Prashanth Prithviraj, Christian Mueller, Chrystelle Brignone, Frederic Triebel

Research outputs 2014 to 2021

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab. METHODS: The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine …

The Prognostic Impact Of Circulating Tumour Dna In Melanoma Patients Treated With Systemic Therapies—Beyond Braf Mutant Detection, Gabriela Marsavela, Peter A. Johansson, Michelle R. Pereira, Ashleigh C. Mcevoy, Anna L. Reid, Cleo Robinson, Lydia Warburton, Muhammad A. Khattak, Tarek M. Meniawy, Benhur Amanuel, Michael Millward, Nicholas K. Hayward, Melanie R. Ziman, Elin S. Gray, Leslie Calapre

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors …

Galectin - Method For Enhancing Specific Immunotherapies In Cancer Treatment, Peter G. Traber, William L. Redmond, Eliezer Zomer, Anatole Klyosov, Stephanie N. Linch

Technology Transfer - Patents

Methods and compositions of the invention relate to the enhancement of specific immunotherapies in cancer treatment. In particular, aspects of the invention relate to novel approaches to boost immune function using a complex carbohydrate pharmaceutical compound alone or in combination with other targeted immunotherapy to increase the efficacy of immunotherapy of cancer.

Method For Enhancing Specific Immunotherapies In Cancer Treatment, Peter G. Traber, William L. Redmond, Eliezer Zomer, Anatole Klyosov, Stefanie N. Linch

Technology Transfer - Patents

Methods and compositions of the invention relate to the enhancement of specific immunotherapies in cancer treatment. In particular, aspects of the invention relate to novel approaches to boost immune function using a complex carbohydrate pharmaceutical compound alone or in combination with other targeted immunotherapy to increase the efficacy of immunotherapy of cancer.

Cloning And Purification Of Sas0397 From Community Associated Staphylococcus Aureus, Amber Wannemacher, H. Kathleen Dannelly

Symposium 2012

Methicillin resistant Staphylococcus aureus (MRSA) is a unique bacterium that can cause painful abscesses that require surgical treatment and can be confined to the skin surface or burrow into the skin causing life-threatening infections. There are two types of MRSA: hospital associated-MRSA (HA-MRSA) and community associated-MRSA (CA-MRSA). Community associated-MRSA is acquired through direct contact with an infected individual or sharing of personal items and is often seen in locations such as athletic facilities, dormitories, and daycare centers. This study involves cloning and purification of SAS0397, a putative exported protein predicted, according to bioinformatics, to be unique to community associated Staphylococcus …

Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator

Department of Biological Sciences Publications

Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative.

Gliotoxin Production In Aspergillus Fumigatus, Susan Musyimi

Theses and Dissertations

Aspergillus fumigalus is a ubiquitous fungus that causes an infection called aspergillosis in immune-compromised surgery patients (Latge, 2001, 384; Bok et al. 2006). Aspergillosis cases have increased in the past decade due to the increasing number of patients undergoing immunosuppressive therapy and receiving organ transplants (Bok et al. 2006). Although there is still disagreement as to the causative agent of the symptoms accompanying aspergillosis, many scientists suspect that the compound, gliotoxin, plays a major role, hi this study, we compared the amounts of gliotoxin produced from clinical and environmental isolates of A. fumigatus. We hypothesized that the amount of gliotoxin …

Suppressive Effects Of Transforming Factor-Β And Interleukin-10 On The Cytolytic Activity Of Murine Macrophages And Reversal By Cytokines, Chin-Hung Lin

Loma Linda University Electronic Theses, Dissertations & Projects

In this study, the suppressive effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on peritoneal macrophage killing of H238 target cells and the potential for reversal of the immunosuppressive effect by IL-4 and interferon-γ (IFN-γ) were investigated. The responsiveness of naive and peptone-activated macrophages was compared. The cytolytic activity for tumor cells of these effector cells was measured by percent lysis of ³H-thymidine labeled Herpes simplex virus type 2-transformed tumor cells (H238). After 18-24 hours of incubation with TGF-β or IL-10, the cytolytic activity of macro-medium alone. The immunosuppressive effect of TGF-β or IL-10 on non-activated macrophages was …

A Phase Ii Trial Of Murine Monoclonal Antibody 17-1a And Interferon-Γ: Clinical And Immunological Data, Mansoor Saleh, Albert Lobuglio, Richard Wheeler, Kimberly Rogers, Amy Haynes, Jeannette Lee, M B. Khazaeli

Haematology and Oncology, East Africa

A group of 15 patients with metastatic colorectal adenocarcinoma received a combination of interferon γ (0.1 mg/m², days 1–15) and the murine monoclonal antibody 17-1A (400 mg, days 5, 7, 9 and 12). The treatment was tolerated with minimal toxicity. Of the 14 evaluable patients, 13 developed human antibody to murine 17-1A, with 11 patients demonstrating antibody to the variable region of 17-1A (anti-idiotype). Antibody to the variable region was inhibited by 17-1A but not by mouse immunoglobulin. Sera from patients with substantial anti-idiotype reactivity were capable of inhibiting the binding of murine 17-1A to antigen expressing LS174-T …

Quinidine-Induced Immune Thrombocytopenia, Mansoor Saleh, Nadhav Dhodaphar, Karren Allen, Albert Lobuglio

Haematology and Oncology, East Africa

D rugs may cause thrombocytopenia by three principal mechanisms: suppression of platelet production, direct platelet toxicity, or antibody-mediated platelet destmction (1). With the advent of assays specifically capable of detecting and quantifying IgG on the platelet surface (2), it has become increasingly possible to recognize cases of drug-induced immune thrombocytopenia based on the detection of elevated levels of platelet surface bound IgG in association with ingestion of causative dmgs. Consequendy, dmg-induced immune thrombocytopenia is no longer a disease diagnosed primarily by exclusion. The occurrence of quinidine-induced thrombocytopenia, though uncommon, was documented as early as 1965 (3) and has been thought …