Immunotherapy Commons^™

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 …

Augmenting Guadecitabine To Promote Anticancer Immunity In Murine Breast Cancer, Timothy M. Smith Jr.

Theses and Dissertations

In immune-competent individuals, tumor growth occurs due to a failure of the immune system to recognize and destroy malignant cells. Immune surveillance can be curtailed by the presence of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) which both serve to dampen antitumor immunity. These studies utilize a metronomic low-dose therapeutic approach to examine the effects of anticancer drugs against murine breast cancer and the effects on the immune cell compartments. The focus of these studies revolve around the drug guadecitabine (guad), a second-generation DNA methyl-transferase inhibitor (DNMTi). DNMTi’s have been shown to dysregulate the methylation …

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 …

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 …

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.

More Haste, Less Speed: Could Public-Private Partnerships Advance Cellular Immunotherapies?, Tania M. Bubela, Katherine Bonter, Silvy Lachance, Jean-Sébastien Delisle, E Richard Gol

Office of the Provost

Cellular immunotherapies promise to transform cancer care. However, they must overcome serious challenges, including: (1) the need to identify and characterize novel cancer antigens to expand the range of therapeutic targets; (2) the need to develop strategies to minimize serious adverse events, such as cytokine release syndrome and treatment-related toxicities; and (3) the need to develop efficient production/manufacturing processes to reduce costs. Here, we discuss whether these challenges might better be addressed through forms of public-private research collaborations, including public-private partnerships (PPPs), or whether these challenges are best addressed by way of standard market transactions. We reviewed 14 public-private relationships …

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.

Sap Is Required For The Development Of Innate Phenotype In H2-M3-Restricted Cd8+ T Cells, Yaw Bediako, Yao Bian, Hong Zhang, Hoonsik Cho

University Faculty Publications and Creative Works

H2-M3-restricted T cells have a preactivated surface phenotype, rapidly expand, and produce cytokines upon stimulation, and, as such, are classified as innate T cells. Unlike most innate T cells, M3-restricted T cells also express CD8ab coreceptors and a diverse TCR repertoire: hallmarks of conventional MHC Ia-restricted CD8+ T cells. Although invariant NKT cells are also innate T cells, they are selected exclusively on hematopoietic cells (HC), whereas M3-restricted T cells can be selected on either hematopoietic or thymic epithelial cells. Moreover, their phenotypes differ depending on what cells mediate their selection. Although there is a clear correlation between selection on …

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 …

Evidence For The Elevation Of Serum Carcinoembryonic Antigen And Tumor-Associated Glycoprotein-72 Levels In Patients Administered Interferons, John Greiner, Fiorella Guadagni, David Goldstein, Ernest Borden, Roy Ritts, Patricia Witt, Albert Lobuglio, Mansoor Saleh, Jeffrey Schlom

Haematology and Oncology, East Africa

Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-γ or IFN-βser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.g., hairy cell leukemia, melanoma) had positive titers of TAG-72 or CEA, and interferon neither increased nor resulted in the appearance of either tumor antigen in those sera. In contrast, 59.2% and …

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 …