Immune Response

This study evaluates whether a mobile phone-based mHealth Behavioural Change Communication BCC educational intervention can improve the adoption and exclusive use of Liquid Petroleum Gas LPG for cooking among households in semi-rural Bangladesh. Household air pollutants HAP from biomass fuels such as wood, agricultural residue, and cow dung expose almost 3 billion people worldwide, including 89% of people in Bangladesh. In the earlier GEOHealth study, 24 months of LPG use reduced personal PM2.5 exposure by about 58.2% and produced changes in innate immune and inflammatory responses, while chronic cardio-pulmonary markers remained relatively stable. More than 70% of households continued using LPG after the earlier study, although not exclusively. The investigators will conduct a large household-level randomized controlled trial using an mHealth-based educational intervention and will continue following the cohort. The study will examine the long-term effects of HAP reduction on subclinical measures of cardiovascular and pulmonary dysfunction, innate and inflammatory immune function, and antibody response to vaccines. Personal 24-hour and area-wise 5-day exposure to PM2.5 and black carbon will be repeatedly assessed before and after the intervention. Lung function and lung pathology will be assessed using spirometry, Chest X-ray, and high-resolution computed tomography of the chest. Cardiovascular measures will include blood pressure and EKG, while metabolic dysfunction will be assessed using HbA1c and fasting lipid profile. Immune function will be evaluated through immune cell phenotyping, functional cytotoxic killer cells, and oxidative stress of lymphocytes.

Researchers are evaluating the use of 68Ga-grazytracer PET imaging to help diagnose pseudoprogression in lung cancer patients after immunotherapy. Pseudoprogression is difficult to distinguish with current clinical methods, which often require follow-up observations that may not meet clinical needs. This study aims to assess the effectiveness and feasibility of this novel imaging agent, which targets granzyme B to show the activity of cytotoxic T cells in tumor areas. This observational study uses 68Ga-grazytracer PETCT scans to visualize and semi-quantitatively measure granzyme B concentration in lung cancer lesions that have enlarged or developed new lesions after immune checkpoint inhibitor treatment. The study follows patients for 4-8 weeks, up to a maximum of 12 weeks, to evaluate the diagnostic performance of this imaging method in detecting pseudoprogression. Participants will undergo PETCT imaging and be monitored over the follow-up period to assess changes and outcomes. Researchers will collect data on diagnostic accuracy and safety during this time. The study includes adult lung cancer patients aged 18 to 75 years who meet specific clinical criteria and have a life expectancy of at least six months. Total participation duration varies with the follow-up period, and patient compliance with study requirements is monitored throughout.

Researchers are investigating how the medicine Filgotinib works to relieve pain in patients with moderate to severe active rheumatoid arthritis RA. This study focuses on understanding two main factors influencing pain relief brain pathways linked to central nervous system sensitization seen in fibromyalgia, and the inflammation surrounding joints and related immune signals. The study aims to clarify why Filgotinib may provide faster pain relief compared to other treatments by examining these mechanisms. Participants prescribed Filgotinib will be observed using advanced 7 Tesla MRI brain imaging to measure changes in brain connectivity and glutamate levels associated with pain processing. The study will assess Filgotinibs impact on both central nervous system pain pathways and peripheral inflammation over periods of up to 12 weeks. This observational test-retest design does not involve altering prescribed treatments but focuses on detailed imaging and biological assessments. During the study, participants will undergo brain MRIs and evaluations of joint inflammation through ultrasound and blood tests measuring cytokines and chemokines. They will also complete questionnaires on pain, fatigue, anxiety, sleep, and cognitive function. Researchers will monitor changes in these measures at intervals up to 12 weeks to understand how Filgotinib affects pain and related symptoms. Total participation time aligns with the 12-week observation period.

Researchers are studying the stimulator of interferon gene STING protein, which plays an important role in the immune systems ability to detect tumors. This trial focuses on evaluating a new imaging agent called 68GaGa-Sa-DABI-4, designed to noninvasively detect STING expression in the tumor environment using positron emission tomography PET. The study aims to assess the safety, distribution in the body, and potential usefulness of this imaging agent for cancer patients. Participants will receive one intravenous injection of the investigational drug 68GaGa-Sa-DABI-4 during the study. This single administration is followed by PET imaging to monitor how the agent interacts with the tumor. The study is conducted in an early phase 1 design, focusing on initial safety and diagnostic capabilities. During the trial, participants will undergo PET scans to evaluate the diagnostic effectiveness of the imaging agent within 15 days after injection. Researchers will monitor safety and how the drug distributes throughout the body. The study includes patients suspected of having or newly diagnosed with malignant diseases. Participation involves a single dosing and imaging session, with safety and diagnostic data collected during this period.

Researchers are evaluating a personalized self-DC vaccine that targets neo-antigens Neo-DC vaccine for treating advanced solid tumors, including head and neck cancer and certain types of non-small cell lung cancer without driver gene mutations. This study aims to explore the dose-limiting toxicity and identify the recommended dose for future Neo-DC vaccine research. About 9 patients will be enrolled, following a 3 plus 3 dose escalation design with two dose levels. Participants will receive infusions of the Neo-DC vaccine at either a lower dose 1 x 107 cells per infusion or a higher dose 5 x 107 cells per infusion given every 7 days. Four infusions make up one treatment cycle. If clinical benefit or certain immune responses are observed, treatment cycles may continue until four administrations are completed, disease progression occurs, new anti-tumor treatments begin, or treatment is stopped for other reasons. Dose-limiting toxicity is monitored within 28 days after the first infusion. During the study, participants will be monitored for adverse events within 28 days of the first vaccine infusion. Researchers will also assess the objective response rate over up to 2 years and observe dose-limiting toxicities in the same 28-day window. Participants must complete all study procedures, including blood collections and tumor assessments based on RECIST 1.1 standards. The total participation duration varies depending on treatment continuation and disease status.

Researchers are studying a new treatment approach for patients with surgically removable head and neck squamous cell carcinoma HNSCC, a common and serious type of cancer in the head and neck region. The study evaluates the safety and tolerability of combining immune-targeted therapy with a lysogenic herpes simplex virus HSV as a neoadjuvant treatment to reduce tumor size before surgery. This innovative combination aims to improve surgery outcomes and lower the chances of cancer returning or spreading. Participants receive a combination of treatments including Tislelizumab given on days 1 and 22, and continuous daily Afatinib from days 1 to 42. They also receive injections of the lysogenic HSV virus directly into lymph nodes, with dosing based on lymph node size, given twice two weeks apart. After these treatments, patients undergo standard surgical removal of the tumor. The HSV virus injection includes an initial dose-escalation phase followed by a dose-expansion phase to find the most effective dose. During the study, patients are closely monitored for side effects and treatment tolerance, including checking for dose-limiting toxicities during surgery. Researchers will assess how well the tumor responds to treatment by examining major and complete pathological responses and overall tumor shrinkage up to eight weeks after treatment. They will also monitor adverse events for up to 12 weeks and follow disease-free survival for one year. The study duration and procedures are planned to provide detailed information on the safety and effects of this combined therapy.

Researchers are evaluating the safety and effectiveness of tumor infiltrating lymphocyte TIL therapy in adults with advanced solid tumors. This early-phase study involves patients who have either relapsed, metastasized, or have primary solid tumors and have failed standard treatments or have no standard options available. The study focuses on patients with measurable tumors and a life expectancy of more than three months. Participants receive an infusion of their own expanded TILs, ranging from 1 billion to 50 billion cells, administered intravenously over 30 to 120 minutes. Before the infusion, patients undergo a non-myeloablative lymphodepletion treatment with hydroxychloroquine a single 600 mg dose and cyclophosphamide. The therapy is given after tumor tissue or malignant fluid is collected for TIL expansion. Throughout the study, participants are closely monitored for adverse events over six months and assessed for tumor response, disease control, duration of response, progression-free survival, and overall survival for up to 36 months. Quality of life changes are also evaluated during this period. Participants must adhere to follow-up visits and assessments to track treatment effects and safety over time.

Researchers are investigating treatments for locally advanced rectal cancer in this national, multicenter, randomized, placebo-controlled Phase III clinical trial. The study aims to evaluate whether combining immunotherapy with total neoadjuvant therapy TNT offers better benefits than long-course radiotherapy followed by TNT alone. It also compares the effectiveness and side effects of different radiotherapy types when combined with immunotherapy under TNT. Participants are assigned to one of three groups one receives short-course radiotherapy SCRT followed by immunotherapy and chemotherapy another receives long-course radiotherapy LCRT with concurrent chemotherapy plus immunotherapy and chemotherapy and the third group receives LCRT with concurrent chemotherapy followed by TNT chemotherapy and a placebo instead of immunotherapy. Immunotherapy or placebo is given via intravenous infusion every three weeks for six cycles. After neoadjuvant therapy, patients may undergo surgery or opt for a watch-and-wait approach if they achieve complete remission. During the study, participants undergo dynamic monitoring including MRI and blood tests to track tumor response and minimal residual disease, especially for tumors close to the anal verge. Researchers assess outcomes such as event-free survival over three years, complete response rates, overall survival, and treatment side effects using standardized criteria. The trial includes follow-up visits and safety evaluations over several years to monitor long-term effects and treatment results.

Researchers are investigating a combination of zoledronic acid and interleukin 2 that boosts a specific immune cell subset called Vb32Vb42 T cells, alongside standard anti-tuberculosis chemotherapy, to treat multidrug-resistant tuberculosis MDR-TB. MDR-TB is a serious form of drug-resistant TB with limited cure rates despite current treatments. This study explores immunotherapy as a new approach to help patients who respond poorly to existing drug regimens. Participants receive treatment following WHO guidelines for drug-resistant TB. One group gets standard MDR-TB treatment plus intravenous zoledronic acid three times and subcutaneous recombinant human interleukin 2 ten times over six months. The other group receives only the standard MDR-TB treatment regimen. The immunotherapy aims to expand and activate Vb32Vb42 T cells to better fight the infection. During the study, researchers monitor participants for changes in sputum smear and culture results, with an average follow-up of 24 months. They also assess lung changes through radiographic imaging over this period. The study collects data on immune response and treatment effectiveness while following participants closely to evaluate safety and disease progression from start to completion.

Researchers are conducting a first-in-human phase 1 trial to study OX118, a human monoclonal antibody targeting OX40 ligand, in healthy adults aged 18 to 60 years. The trial aims to evaluate the safety, tolerability, and how the body processes OX118 when given as a single intravenous dose. This study involves 32 healthy volunteers with a body mass index between 18.5 and 30.0. Participants are divided into five groups receiving different single doses of OX118 or a placebo by intravenous infusion. The doses range from 0.1 mgkg to 10 mgkg, with participants randomized to receive either the drug or placebo based on a pre-arranged schedule. The trial includes sentinel dosing for initial participants in each group, and all participants stay at the clinic for at least 24 hours after dosing for monitoring. Each participant will attend 7 clinic visits over about 91 days, including a 28-day screening period. Visits include treatment administration, safety assessments such as vital signs, ECGs, physical exams, laboratory tests, and monitoring for adverse events. Safety data is reviewed by an internal committee before moving to the next dosing group. Researchers will measure adverse events, vital signs, lab results, ECG changes, and physical exam findings from Day 1 to Day 63, along with drug concentration and immune response data.