John E. Connolly
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View article: Enabling access to genetically modified cell therapies through flexible approaches to manufacturing and cost recovery
Enabling access to genetically modified cell therapies through flexible approaches to manufacturing and cost recovery Open
Genetically modified cell-based therapies hold transformative potential, particularly for patients with rare cancers and ultra-rare diseases. However, progress toward regulatory approval, reimbursement, and broad patient access is often co…
View article: Investigating the influence of baseline medications on immune checkpoint inhibitor treatment outcomes for cancer patients 3706
Investigating the influence of baseline medications on immune checkpoint inhibitor treatment outcomes for cancer patients 3706 Open
Description Immune checkpoint inhibitors (ICIs) are first-line treatment options for many cancer patients. However, ICI treatment resistance and risk of immune-mediated toxicities continue to impact therapeutic success. Concomitant medicat…
View article: Intentional heterogeneity in autologous cell-based gene therapies: strategic considerations for first-in-human trials
Intentional heterogeneity in autologous cell-based gene therapies: strategic considerations for first-in-human trials Open
Cell-based gene therapies, including chimeric antigen receptor-T, T-cell receptor-T, and tumor-infiltrating lymphocyte therapies, have transformed the treatment landscape for certain cancers, yet their efficacy in solid tumors remains limi…
View article: Changes in Payer Mix Associated With Private Equity Acquisition of Ophthalmology Practices
Changes in Payer Mix Associated With Private Equity Acquisition of Ophthalmology Practices Open
This cross-sectional study examines the changes in payer mix associated with private equity acquisition of opthamology practices in the US.
View article: Associations between immune checkpoint inhibitor response, immune-related adverse events, and steroid use in RADIOHEAD: a prospective pan-tumor cohort study
Associations between immune checkpoint inhibitor response, immune-related adverse events, and steroid use in RADIOHEAD: a prospective pan-tumor cohort study Open
Background Immune checkpoint inhibitors (ICIs) have led to enduring responses in subsets of patients with cancer. However, these responses carry the risk of immune-related adverse events (irAEs), which can diminish the overall benefit of I…
View article: Molecular analysis of acute pyelonephritis—excessive innate and attenuated adaptive immunity
Molecular analysis of acute pyelonephritis—excessive innate and attenuated adaptive immunity Open
This study investigated the molecular basis of disease severity in acute pyelonephritis (APN), a common and potentially life-threatening bacterial infection. Two cohorts of infants with febrile urinary tract infection were included. Renal …
View article: Tumour-derived extracellular vesicles within the therapy-induced senescent secretome distinctly suppress breast cancer via DKK1-mediated inflammatory response
Tumour-derived extracellular vesicles within the therapy-induced senescent secretome distinctly suppress breast cancer via DKK1-mediated inflammatory response Open
Triple-negative breast cancers (TNBC), associated with poor prognosis and high tumour recurrence, are often-treated with taxanes in first-line treatment regimens. However, acquired disease resistance can often set in, hampering clinical ef…
View article: A novel GPI-anchored dominant-negative TGF-β receptor II renders T cells unresponsive to TGF-β signaling
A novel GPI-anchored dominant-negative TGF-β receptor II renders T cells unresponsive to TGF-β signaling Open
Transforming growth factor β (TGF-β) is a pleiotropic cytokine expressed by a wide range of cell types and is known for hampering the effectiveness of cancer immune cell therapeutic approaches. We have designed a novel construct containing…
View article: Themis controls T cell activation, effector functions, and metabolism of peripheral CD8<sup>+</sup>T cells
Themis controls T cell activation, effector functions, and metabolism of peripheral CD8<sup>+</sup>T cells Open
Themis is important in regulating positive selection of thymocytes during T cell development, but its role in peripheral T cells is less understood. Here, we investigated T cell activation and its sequelae using a tamoxifen-mediated, acute…
View article: An Exploratory Study Investigating the Prevalence of Gastrointestinal Symptoms in Collegiate Division I American Football Athletes
An Exploratory Study Investigating the Prevalence of Gastrointestinal Symptoms in Collegiate Division I American Football Athletes Open
Gastrointestinal (GI) symptoms may limit performance, but their prevalence and impact among team sports athletes is not well-documented. The objective of this study was to examine the prevalence of GI symptoms in a small sample of collegia…
View article: Platelet TLR7 is essential for the formation of platelet–neutrophil complexes and low-density neutrophils in lupus nephritis
Platelet TLR7 is essential for the formation of platelet–neutrophil complexes and low-density neutrophils in lupus nephritis Open
Objectives Platelets and low-density neutrophils (LDNs) are major players in the immunopathogenesis of SLE. Despite evidence showing the importance of platelet–neutrophil complexes (PNCs) in inflammation, little is known about the relation…
View article: Data from Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells
Data from Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells Open
Acute myeloid leukemia (AML) is an aggressive disease with poor outcomes, overwhelmingly due to relapse. Minimal residual disease (MRD), defined as the persistence of leukemic cells after chemotherapy treatment, is thought to be the major …
View article: Data from Autophagy Governs Protumorigenic Effects of Mitotic Slippage–induced Senescence
Data from Autophagy Governs Protumorigenic Effects of Mitotic Slippage–induced Senescence Open
The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding …
View article: Data from Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells
Data from Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells Open
Acute myeloid leukemia (AML) is an aggressive disease with poor outcomes, overwhelmingly due to relapse. Minimal residual disease (MRD), defined as the persistence of leukemic cells after chemotherapy treatment, is thought to be the major …
View article: Supplementary Data from Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells
Supplementary Data from Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells Open
Pathology report
View article: First-in-Human Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Rapidly Developed SARS-CoV-2 Therapeutic Antibody, AOD01, in Healthy Adults
First-in-Human Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Rapidly Developed SARS-CoV-2 Therapeutic Antibody, AOD01, in Healthy Adults Open
AOD01 was safe and well tolerated, demonstrated dose-related PK, non-immunogenic status, and sustained ex vivo neutralization of SARS-CoV-2 after single intravenous dose ranging from 2 to 20 mg/kg and two doses of 20 mg/kg and show good po…
View article: ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome
ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome Open
Human NLRP1 (NACHT, LRR, and PYD domain-containing protein 1) is an innate immune sensor predominantly expressed in the skin and airway epithelium. Here, we report that human NLRP1 senses the ultraviolet B (UVB)- and toxin-induced ribotoxi…
View article: Human NLRP1 is activated by ZAKɑ-driven ribotoxic stress response
Human NLRP1 is activated by ZAKɑ-driven ribotoxic stress response Open
Human NLRP1 is a multifunctional inflammasome sensor predominantly expressed in skin and airway epithelium; however its function in skin-specific immunity and its mechanisms of activation are not fully understood. Here we report that human…
View article: Dysfunctional Bronchial Cilia Are a Feature of Chronic Obstructive Pulmonary Disease (COPD)
Dysfunctional Bronchial Cilia Are a Feature of Chronic Obstructive Pulmonary Disease (COPD) Open
Impaired mucociliary clearance may increase COPD exacerbation risk. We aimed to compare bronchial ciliary function and epithelial ultrastructure of COPD patients to healthy controls and explore its relationship to exacerbator phenotypes (f…
View article: Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in cynomolgus macaques are modulated by strain-specificity within the Asian lineage
Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in cynomolgus macaques are modulated by strain-specificity within the Asian lineage Open
Zika virus (ZIKV) is an emerging arbovirus with recent global expansion. Historically, ZIKV infections with Asian lineages have been associated with mild disease such as rash and fever. However, recent Asian sub-lineages have caused outbre…
View article: A Perspective on Cell Therapy and Cancer Vaccine in Biliary Tract Cancers (BTCs)
A Perspective on Cell Therapy and Cancer Vaccine in Biliary Tract Cancers (BTCs) Open
Biliary tract cancer (BTC) is a rare, but aggressive, disease that comprises of gallbladder carcinoma, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with heterogeneous molecular profiles. Advanced disease has limited…
View article: Dominant-negative NFKBIA mutation promotes IL-1β production causing hepatic disease with severe immunodeficiency
Dominant-negative NFKBIA mutation promotes IL-1β production causing hepatic disease with severe immunodeficiency Open
Although IKK-β has previously been shown as a negative regulator of IL-1β secretion in mice, this role has not been proven in humans. Genetic studies of NF-κB signaling in humans with inherited diseases of the immune system have not demons…