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Immunotherapy

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Articles 1 - 30 of 369

Full-Text Articles in Medicine and Health Sciences

Aducanumab Anti-Amyloid Immunotherapy Induces Sustained Microglial And Immune Alterations, Mika P Cadiz, Katelin A Gibson, Kennedi T Todd, David G Nascari, Nashali Massa, Meredith T Lilley, Kimberly C Olney, Md Mamun Al-Amin, Hong Jiang, David M Holtzman, John D Fryer Feb 2024

Aducanumab Anti-Amyloid Immunotherapy Induces Sustained Microglial And Immune Alterations, Mika P Cadiz, Katelin A Gibson, Kennedi T Todd, David G Nascari, Nashali Massa, Meredith T Lilley, Kimberly C Olney, Md Mamun Al-Amin, Hong Jiang, David M Holtzman, John D Fryer

2020-Current year OA Pubs

Aducanumab, an anti-amyloid immunotherapy for Alzheimer's disease, efficiently reduces Aβ, though its plaque clearance mechanisms, long-term effects, and effects of discontinuation are not fully understood. We assessed the effect of aducanumab treatment and withdrawal on Aβ, neuritic dystrophy, astrocytes, and microglia in the APP/PS1 amyloid mouse model. We found that reductions in amyloid and neuritic dystrophy during acute treatment were accompanied by microglial and astrocytic activation, and microglial recruitment to plaques and adoption of an aducanumab-specific pro-phagocytic and pro-degradation transcriptomic signature, indicating a role for microglia in aducanumab-mediated Aβ clearance. Reductions in Aβ and dystrophy were sustained 15 but not …


Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila Kunuthuru Jan 2024

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila Kunuthuru

Auctus: The Journal of Undergraduate Research and Creative Scholarship

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. …


Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates Dec 2023

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …


Circulating Pre-Treatment T-Cell Receptor Repertoire As A Predictive Biomarker In Advanced Or Metastatic Non-Small-Cell Lung Cancer Patients Treated With Pembrolizumab Alone Or In Combination With Chemotherapy, A. Abed, Aaron B. Beasley, Anna L. Reid, N. Law, L. Calapre, M. Millward, Johnny Lo, Elin S. Gray Dec 2023

Circulating Pre-Treatment T-Cell Receptor Repertoire As A Predictive Biomarker In Advanced Or Metastatic Non-Small-Cell Lung Cancer Patients Treated With Pembrolizumab Alone Or In Combination With Chemotherapy, A. Abed, Aaron B. Beasley, Anna L. Reid, N. Law, L. Calapre, M. Millward, Johnny Lo, Elin S. Gray

Research outputs 2022 to 2026

Background: The circulating T-cell receptor (TCR) repertoire is a dynamic representation of overall immune responses in an individual. Materials and methods: We prospectively collected baseline blood from patients treated with first-line pembrolizumab monotherapy or in combination with chemotherapy. TCR repertoire metrics were correlated with clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). We built a logistic regression classifier by fitting all four TCR- repertoire metrics to the immune checkpoint inhibitor (ICI) CBR data. In the subsequent receiver operating characteristic (ROC) analysis of the resulting logistic regression model probabilities, the best cut-off value was …


Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn Nov 2023

Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn

Faculty Journal Articles

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and …


Advancements In Dendritic Cell Vaccination: Enhancing Efficacy And Optimizing Combinatorial Strategies For The Treatment Of Glioblastoma, Robert Subtirelu, Eric Teichner, Arjun Ashok, Chitra Parikh, Sahithi Talasila, Irina-Mihaela Matache, Ahab Alnemri, Victoria Anderson, Osmaan Shahid, Sricharvi Mannam, Andrew Lee, Thomas Werner, Mona-Elisabeth Revheim, Abass Alavi Oct 2023

Advancements In Dendritic Cell Vaccination: Enhancing Efficacy And Optimizing Combinatorial Strategies For The Treatment Of Glioblastoma, Robert Subtirelu, Eric Teichner, Arjun Ashok, Chitra Parikh, Sahithi Talasila, Irina-Mihaela Matache, Ahab Alnemri, Victoria Anderson, Osmaan Shahid, Sricharvi Mannam, Andrew Lee, Thomas Werner, Mona-Elisabeth Revheim, Abass Alavi

Student Papers, Posters & Projects

Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of …


Xaluritamig, A Steap1 × Cd3 Xmab 2+1 Immune Therapy For Metastatic Castration-Resistant Prostate Cancer: Results From Dose Exploration In A First-In-Human Study, William K. Kelly, Daniel C. Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J. Ward, Andrew J. Armstrong, David Pook, Miso Kim, Tanya B. Dorff, Stefanie Fischer, Yung-Chang Lin, Lisa G. Horvath, Christopher Sumey, Zhao Yang, Gabor Jurida, Kristen M. Smith, Jamie N. Connarn, Hweixian L. Penny, Julia Stieglmaier, Leonard J. Appleman Oct 2023

Xaluritamig, A Steap1 × Cd3 Xmab 2+1 Immune Therapy For Metastatic Castration-Resistant Prostate Cancer: Results From Dose Exploration In A First-In-Human Study, William K. Kelly, Daniel C. Danila, Chia-Chi Lin, Jae-Lyun Lee, Nobuaki Matsubara, Patrick J. Ward, Andrew J. Armstrong, David Pook, Miso Kim, Tanya B. Dorff, Stefanie Fischer, Yung-Chang Lin, Lisa G. Horvath, Christopher Sumey, Zhao Yang, Gabor Jurida, Kristen M. Smith, Jamie N. Connarn, Hweixian L. Penny, Julia Stieglmaier, Leonard J. Appleman

Kimmel Cancer Center Faculty Papers

ABSTRACT : Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during …


Prostate Cancer Immunotherapy: Improving Clinical Outcomes With A Multi-Pronged Approach, Dhivya Sridaran, Elliot Bradshaw, Carl Deselm, Russell Pachynski, Kiran Mahajan, Nupam P Mahajan Oct 2023

Prostate Cancer Immunotherapy: Improving Clinical Outcomes With A Multi-Pronged Approach, Dhivya Sridaran, Elliot Bradshaw, Carl Deselm, Russell Pachynski, Kiran Mahajan, Nupam P Mahajan

2020-Current year OA Pubs

Cancer immunotherapy has gained traction in recent years owing to remarkable tumor clearance in some patients. Despite the notable success of immune checkpoint blockade (ICB) in multiple malignancies, engagement of the immune system for targeted prostate cancer (PCa) therapy is still in its infancy. Multiple factors contribute to limited response, including the heterogeneity of PCa, the cold tumor microenvironment, and a low number of neoantigens. Significant effort is being invested in improving immune-based PCa therapies. This review is a summary of the status of immunotherapy in treating PCa, with a discussion of multiple immune modalities, including vaccines, adoptively transferred T …


Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu Oct 2023

Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu

Research Colloquium

Introduction: About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in other cancers but limited response in pancreatic cancer due to desmoplasia and fibrotic tumor microenvironment. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. Due to its high membrane expression, MUC13 may serve as an excellent target …


A Novel Approach To Target Tumor Immune Microenvironment And Improve Checkpoint Immunotherapies, Poornima Devi Shaji, Ana Martinez, Melida Flores Cantu, Anupam Dhasmana, Meena Jaggi, Stephen W. Behrman, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan Oct 2023

A Novel Approach To Target Tumor Immune Microenvironment And Improve Checkpoint Immunotherapies, Poornima Devi Shaji, Ana Martinez, Melida Flores Cantu, Anupam Dhasmana, Meena Jaggi, Stephen W. Behrman, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan

Research Colloquium

Background: Pancreatic cancer remains 3rd deadliest disease, with less than 7-10% survival rate. Little progress has been seen in patient’s outcome due to high desmoplasia and chemo-resistance. Immunotherapy has shown promising results in cancers, except pancreatic cancer due to their characteristic fibrotic tumor microenvironment. The therapies are unable to penetrate fibrotic tumor leading to insufficient availability of therapeutic drugs at the tumor site. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas, that makes it an excellent protein tumor target. This study is unique as it utilizes MUC13Ab for targeting the pancreatic …


Extracellular Vesicles In Triple–Negative Breast Cancer: Immune Regulation, Biomarkers, And Immunotherapeutic Potential, Kaushik Das, Subhojit Paul, Arnab Ghosh, Saurabh Gupta, Tanmoy Mukherjee, Prem Shankar, Anshul Sharma, Shiva Keshava, Subhash C. Chauhan, Vivek Kumar Kashyap Oct 2023

Extracellular Vesicles In Triple–Negative Breast Cancer: Immune Regulation, Biomarkers, And Immunotherapeutic Potential, Kaushik Das, Subhojit Paul, Arnab Ghosh, Saurabh Gupta, Tanmoy Mukherjee, Prem Shankar, Anshul Sharma, Shiva Keshava, Subhash C. Chauhan, Vivek Kumar Kashyap

School of Medicine Publications and Presentations

Triple–negative breast cancer (TNBC) is an aggressive subtype accounting for ~10–20% of all human BC and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) amplification. Owing to its unique molecular profile and limited targeted therapies, TNBC treatment poses significant challenges. Unlike other BC subtypes, TNBC lacks specific molecular targets, rendering endocrine therapies and HER2–targeted treatments ineffective. The chemotherapeutic regimen is the predominant systemic treatment modality for TNBC in current clinical practice. However, the efficacy of chemotherapy in TNBC is variable, with response rates varying between a wide range …


Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser Oct 2023

Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser

Electronic Theses, Projects, and Dissertations

Glioblastoma multiforme is the most aggressive type of glioma, demonstrating extremely low long-term survival despite modern therapies. Chimeric antigen receptor T cells have shown extreme levels of success in the treatment of B cell lymphomas through persistent anti-tumor activity. Prior research has demonstrated the therapeutic potential in targeting the C3a-C3aR1 pathway as it acts in an autocrine loop, maintaining the proliferation and survival of cancer stem cells within the tumor. Here, we reorient the treatment to target C3aR1 for the treatment of glioblastoma multiforme. In order to achieve this, Jurkat immortalized T cells will express various chimeric antigen receptor designs …


Immunepotent Crp Enhances Cyclophosphamide-Induced Cytotoxicity Through A Caspase Independent But Ros Dependent Mechanism In Triple Negative-Breast Cancer Cells, Ana L. Rivera, A. C. Martínez-Torres, C. Rodríguez-Padilla Sep 2023

Immunepotent Crp Enhances Cyclophosphamide-Induced Cytotoxicity Through A Caspase Independent But Ros Dependent Mechanism In Triple Negative-Breast Cancer Cells, Ana L. Rivera, A. C. Martínez-Torres, C. Rodríguez-Padilla

Research Symposium

Background: Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CYP) remains a mainstay in cancer therapy mainly in the triple negative breast cancer subtype (TNBC) in spite of harmful adverse effects and cell death-resistances. To face this, combination of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells, beside improving clinical parameters of chemotherapy-treated patients. The aim of this study was to evaluate the mechanism of cytotoxicity induced by ICRP in combination with …


Antibody Mediated Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan Sep 2023

Antibody Mediated Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan, Sheema Khan

Research Symposium

About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in cancers, except pancreatic cancer due to their characteristic fibrotic tumor microenvironment. The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but …


Vegf-B Prevents Excessive Angiogenesis By Inhibiting Fgf2/Fgfr1 Pathway, Chunsik Lee, David M Ornitz, Et Al. Aug 2023

Vegf-B Prevents Excessive Angiogenesis By Inhibiting Fgf2/Fgfr1 Pathway, Chunsik Lee, David M Ornitz, Et Al.

2020-Current year OA Pubs

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting …


The Evolving Landscape Of Immunotherapy For The Treatment Of Allergic Conditions., Aarti Pandya, Esosa Adah, Bridgette Jones, Rachel Chevalier Aug 2023

The Evolving Landscape Of Immunotherapy For The Treatment Of Allergic Conditions., Aarti Pandya, Esosa Adah, Bridgette Jones, Rachel Chevalier

Manuscripts, Articles, Book Chapters and Other Papers

Allergic conditions, such as asthma, chronic urticaria, atopic dermatitis (AD), and eosinophilic esophagitis, have long been treated with oral and topical steroids which resulted in negative off-target effects. However, newer biologic medications are increasingly being developed and approved for treatment of these conditions. These medications have a variety of mechanisms of action to target pathophysiology specific to these diseases. As biologics become more targeted, fewer off-target effects are seen improving tolerability for patients as well as expanded options for treatment of these conditions. This review discusses monoclonal antibody therapies (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, and tralokinumab) including their safety …


Induction Of Cancer Neoantigens Facilitates Development Of Clinically Relevant Models For The Study Of Pancreatic Cancer Immunobiology, Usman Y Panni, Michael Y Chen, Felicia Zhang, Darren R Cullinan, Lijin Li, C Alston James, Xiuli Zhang, S Rogers, A Alarcon, John M Baer, Daoxiang Zhang, Feng Gao, Christopher A Miller, Qingqing Gong, Kian-Huat Lim, David G Denardo, S Peter Goedegebuure, William E Gillanders, William G Hawkins Aug 2023

Induction Of Cancer Neoantigens Facilitates Development Of Clinically Relevant Models For The Study Of Pancreatic Cancer Immunobiology, Usman Y Panni, Michael Y Chen, Felicia Zhang, Darren R Cullinan, Lijin Li, C Alston James, Xiuli Zhang, S Rogers, A Alarcon, John M Baer, Daoxiang Zhang, Feng Gao, Christopher A Miller, Qingqing Gong, Kian-Huat Lim, David G Denardo, S Peter Goedegebuure, William E Gillanders, William G Hawkins

2020-Current year OA Pubs

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint …


Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang Jul 2023

Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.


Perspectives In Immunotherapy: Meeting Report From Immunotherapy Bridge (Naples, November 30th-December 1st, 2022), Paolo A Ascierto, Nathan Singh, Et Al. Jul 2023

Perspectives In Immunotherapy: Meeting Report From Immunotherapy Bridge (Naples, November 30th-December 1st, 2022), Paolo A Ascierto, Nathan Singh, Et Al.

2020-Current year OA Pubs

The discovery and development of novel treatments that harness the patient's immune system and prevent immune escape has dramatically improved outcomes for patients across cancer types. However, not all patients respond to immunotherapy, acquired resistance remains a challenge, and responses are poor in certain tumors which are considered to be immunologically cold. This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. These new approaches are focused on patients with an inadequate response to current treatments, with emerging evidence of improved responses in various cancers with new immunotherapy …


Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil Jun 2023

Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil

USF Tampa Graduate Theses and Dissertations

Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …


Tumor Biology And Immune Infiltration Define Primary Liver Cancer Subsets Linked To Overall Survival After Immunotherapy, Anuradha Budhu, Erica C Pehrsson, Aiwu He, Lipika Goyal, Robin Kate Kelley, Hien Dang, Changqing Xie, Cecilia Monge, Mayank Tandon, Lichun Ma, Mahler Revsine, Laura Kuhlman, Karen Zhang, Islam Baiev, Ryan Lamm, Keyur Patel, David E Kleiner, Stephen M Hewitt, Bao Tran, Jyoti Shetty, Xiaolin Wu, Yongmei Zhao, Tsai-Wei Shen, Sulbha Choudhari, Yuliya Kriga, Kris Ylaya, Andrew C Warner, Elijah F Edmondson, Marshonna Forgues, Tim F Greten, Xin Wei Wang Jun 2023

Tumor Biology And Immune Infiltration Define Primary Liver Cancer Subsets Linked To Overall Survival After Immunotherapy, Anuradha Budhu, Erica C Pehrsson, Aiwu He, Lipika Goyal, Robin Kate Kelley, Hien Dang, Changqing Xie, Cecilia Monge, Mayank Tandon, Lichun Ma, Mahler Revsine, Laura Kuhlman, Karen Zhang, Islam Baiev, Ryan Lamm, Keyur Patel, David E Kleiner, Stephen M Hewitt, Bao Tran, Jyoti Shetty, Xiaolin Wu, Yongmei Zhao, Tsai-Wei Shen, Sulbha Choudhari, Yuliya Kriga, Kris Ylaya, Andrew C Warner, Elijah F Edmondson, Marshonna Forgues, Tim F Greten, Xin Wei Wang

Kimmel Cancer Center Faculty Papers

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field. In a retrospective arm of the National Cancer Institute Cancers of the Liver: Accelerating Research of Immunotherapy by a Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and cholangiocarcinoma patients prior to and following immune checkpoint inhibitor treatment. …


Novel Vaccine Against Pathological Pyroglutamate-Modified Amyloid Beta For Prevention Of Alzheimer's Disease, Karen Zagorski, Olga King, Armine Hovakimyan, Irina Petrushina, Tatevik Antonyan, Gor Chailyan, Manush Ghazaryan, Krzysztof L Hyrc, Jean Paul Chadarevian, Hayk Davtyan, Mathew Blurton-Jones, David H Cribbs, Michael G Agadjanyan, Anahit Ghochikyan Jun 2023

Novel Vaccine Against Pathological Pyroglutamate-Modified Amyloid Beta For Prevention Of Alzheimer's Disease, Karen Zagorski, Olga King, Armine Hovakimyan, Irina Petrushina, Tatevik Antonyan, Gor Chailyan, Manush Ghazaryan, Krzysztof L Hyrc, Jean Paul Chadarevian, Hayk Davtyan, Mathew Blurton-Jones, David H Cribbs, Michael G Agadjanyan, Anahit Ghochikyan

2020-Current year OA Pubs

Post-translationally modified N-terminally truncated amyloid beta peptide with a cyclized form of glutamate at position 3 (pE


Stromal And Therapy-Induced Macrophage Proliferation Promotes Pdac Progression And Susceptibility To Innate Immunotherapy, Chong Zuo, John M Baer, Brett L Knolhoff, Jad I Belle, Xiuting Liu, Angela Alarcon De La Lastra, Graham D Hogg, Natalie L Kingston, Marcus A Breden, Paarth B Dodhiawala, Daniel Cui Zhou, Varintra E Lander, C Alston James, Li Ding, Kian-Huat Lim, Ryan C Fields, William G Hawkins, Jason D Weber, Guoyan Zhao, David G Denardo, Et Al. Jun 2023

Stromal And Therapy-Induced Macrophage Proliferation Promotes Pdac Progression And Susceptibility To Innate Immunotherapy, Chong Zuo, John M Baer, Brett L Knolhoff, Jad I Belle, Xiuting Liu, Angela Alarcon De La Lastra, Graham D Hogg, Natalie L Kingston, Marcus A Breden, Paarth B Dodhiawala, Daniel Cui Zhou, Varintra E Lander, C Alston James, Li Ding, Kian-Huat Lim, Ryan C Fields, William G Hawkins, Jason D Weber, Guoyan Zhao, David G Denardo, Et Al.

2020-Current year OA Pubs

Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling …


Development Of Magnetic Particle Imaging For Quantitative Immune Cell Tracking, Julia J. Gevaert May 2023

Development Of Magnetic Particle Imaging For Quantitative Immune Cell Tracking, Julia J. Gevaert

Electronic Thesis and Dissertation Repository

The Foster lab has been developing cellular MRI tools for well over a decade using superparamagnetic iron oxide (SPIO)-based contrast agents for numerous applications cell tracking applications. SPIO are used to label cells which are indirectly detected as regions of signal loss. The main challenge with this technique is quantification of cell number, which is important for applications such as dendritic cell (DC)-based immunotherapies where cell number is used as a predictor of immunotherapeutic response.

Magnetic particle imaging (MPI) is a novel pre-clinical modality that shows promise for cell tracking. MPI directly detects the nonlinear magnetization response of superparamagnetic iron …


Pustular Psoriasis And The Potential Therapeutic Usage Of An Il-36 Receptor Monoclonal Antibody, Jeannel T. Miclat, Shafik Habal May 2023

Pustular Psoriasis And The Potential Therapeutic Usage Of An Il-36 Receptor Monoclonal Antibody, Jeannel T. Miclat, Shafik Habal

Research Day

Pustular psoriasis is an uncommon subtype of psoriasis that dramatically affects the quality of life of affected patients. Pustules can emerge anywhere along the trunk, limbs, soles, palms, and fingers, which debilitates the functionality of these appendages. Currently, there are no approved treatments for pustular psoriasis in the US; off-label usage of psoriasis vulgaris medications is usually prescribed. These treatments are insufficient for patients with difficult to manage or severe forms of pustular psoriasis. Psoriasis vulgaris biologic medications mainly target the IL-17 and IL-23 axis. However, novel clinical findings have demonstrated that pustular psoriasis’s central inflammatory axis depends on the …


Impact Of Early Relapse Within 24 Months After First-Line Systemic Therapy (Pod24) On Outcomes In Patients With Marginal Zone Lymphoma: A Us Multisite Study, Narendranath Epperla, Rina Li Welkie, Pallawi Torka, Geoffrey Shouse, Reem Karmali, Lauren Shea, Andrea Anampa-Guzmán, Timothy S Oh, Heather Reaves, Montreh Tavakkoli, Kathryn Lindsey, Irl Brian Greenwell, Emily Hansinger, Colin Thomas, Sayan Mullick Chowdhury, Kaitlin Annunzio, Beth Christian, Stefan K Barta, Praveen Ramakrishnan Geethakumari, Nancy L Bartlett, Alex F Herrera, Natalie S Grover, Adam J Olszewski May 2023

Impact Of Early Relapse Within 24 Months After First-Line Systemic Therapy (Pod24) On Outcomes In Patients With Marginal Zone Lymphoma: A Us Multisite Study, Narendranath Epperla, Rina Li Welkie, Pallawi Torka, Geoffrey Shouse, Reem Karmali, Lauren Shea, Andrea Anampa-Guzmán, Timothy S Oh, Heather Reaves, Montreh Tavakkoli, Kathryn Lindsey, Irl Brian Greenwell, Emily Hansinger, Colin Thomas, Sayan Mullick Chowdhury, Kaitlin Annunzio, Beth Christian, Stefan K Barta, Praveen Ramakrishnan Geethakumari, Nancy L Bartlett, Alex F Herrera, Natalie S Grover, Adam J Olszewski

Department of Medicine Faculty Papers

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of …


Impact Of Early Relapse Within 24 Months After First-Line Systemic Therapy (Pod24) On Outcomes In Patients With Marginal Zone Lymphoma: A Us Multisite Study, Narendranath Epperla, Lauren Shea, Nancy L Bartlett, Et Al. May 2023

Impact Of Early Relapse Within 24 Months After First-Line Systemic Therapy (Pod24) On Outcomes In Patients With Marginal Zone Lymphoma: A Us Multisite Study, Narendranath Epperla, Lauren Shea, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of …


Oncolytic Virus Immunotherapy: Development And Potential For Cancer Treatment, Olivia Guinness May 2023

Oncolytic Virus Immunotherapy: Development And Potential For Cancer Treatment, Olivia Guinness

Honors Scholar Theses

The American Cancer Society estimates that in 2023, 1,958,310 new cancer cases and 609,820 cancer deaths will occur in the United States [16]. A promising therapeutic option that has been supported by recent clinical trials is the use of oncolytic viruses to treat malignant tumors. The mechanism of action of existing treatments, such as chemotherapy, radiotherapy, and surgery, differs from that of oncolytic virus therapy because oncolytic viruses are able to affect cancer cells with specificity, minimizing side effects. When infecting a normal, non-cancerous cell, oncolytic viruses do not replicate, leaving healthy cells unaffected. In tumor cells, oncolytic viruses will …


Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li May 2023

Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li

Dissertations & Theses (Open Access)

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NKTROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …


Immunotherapeutic Approach To Reduce Senescent Cells And Alleviate Senescence-Associated Secretory Phenotype In Mice, Niraj Shrestha, Mark Foster, Lynne Marsala, Pamela Wong, Celia C Cubitt, Jennifer A Foltz, Jennifer Tran, Timothy Schappe, Melissa M Berrien-Elliott, Todd A Fehniger, Et Al. May 2023

Immunotherapeutic Approach To Reduce Senescent Cells And Alleviate Senescence-Associated Secretory Phenotype In Mice, Niraj Shrestha, Mark Foster, Lynne Marsala, Pamela Wong, Celia C Cubitt, Jennifer A Foltz, Jennifer Tran, Timothy Schappe, Melissa M Berrien-Elliott, Todd A Fehniger, Et Al.

2020-Current year OA Pubs

Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and …