China
Africa
Explore chapters and articles related to this topic
Drug Repurposing and Novel Antiviral Drugs for COVID-19 Management
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Shailendra Dwivedi, Aakanksha Rawat, Amit Ranjan, Ruchika Agrawal, Radhieka Misra, Sunil Kumar Gupta, Surekha Kishore, Sanjeev Misra
Tocilizumab (TCZ) is another humanized mono- clonal antibody that inhibits the IL-6 receptor. TCZ has been used successfully for the treatment of rheumatoid arthritis and other auto-inflammatory processes. It has also been useful for the treatment of severe cytokine release syndrome (CRS) induced by the chimeric antigen receptor. Consequently, TCZ, an IL-6 receptor blocker, may be suitable for treating patients with severe pneumonia. A recent retrospective, observational study demonstrated that TCZ significantly reduced mortality among 630 COVID-19 patients admitted to an ICU [19]. Another study demonstrated that TCZ decreased mortality and duration of hospital stay in critically ill patients but seemed to have a high risk of serious infections [20]. Similar outcomes were reported in another related study involving 158 severe COVID-19 patients claiming significantly decreased mortality with TCZ [21]. Furthermore, in research carried out by Yale University School of Medicine, reduced need for mechanical ventilation and improved inflammatory biomarkers were noted in patients on TCZ [22]. A study in China revealed that TCZ significantly improved clinical outcomes and reduced mortality among patients with severe COVID-19 [23]. It also reduced the risk of cytokine storms among COVID-19 patients in another study. The abilities of the TCZ to relieve inflammation and cytokine storms among COVID-19 patients were further justified in many meta-analyses [24–26].
AI and Autoimmunity
Published in Louis J. Catania, AI for Immunology, 2021
Chimeric antigen receptor T-cells (CAR-T-cells) are T-cells that have been genetically engineered to give them the new ability to target a specific protein. The receptors are “chimeric” because they combine both antigen-binding and T-cell activating functions into a single receptor. The premise of CAR-T immunotherapy is to modify T-cells to recognize cancer cells to more effectively target and destroy them.56 CAR-T-cell therapy (see Figure 4.1) begins by removing a patient’s T lymphocytes and transducing them with a DNA plasmid vector (a DNA molecule distinct from the cell’s DNA used as a tool to clone, transfer, and manipulate genes)57 that encodes specific tumor antigens. These modified and targeted lymphocytes are then reintroduced to the patient’s body through a single infusion to attack tumor cells. Known as autologous CAR-T-cell therapy, this treatment has been in development for more than 25 years, resulting in four generations of improving therapy that has generated responses for up to four years in some studies.58
The Future of Physical Activity, Rehabilitation, and End-of-Life Care
Published in Amy J. Litterini, Christopher M. Wilson, Physical Activity and Rehabilitation in Life-threatening Illness, 2021
Christopher M. Wilson, Amy J. Litterini
An increasingly common immunotherapy treatment for hematologic cancers is chimeric antigen receptor T-cell therapy (CAR-T), which results in modification of T-cells that can identify and attack the cancer cells. This process is depicted in Figure 23.1. First, T-cells are extracted from the patient’s bloodstream via IV access. After extraction, genetic information for the specific antigen of the cancer cells is encoded into the T-cells. These new CAR receptors found on the surface of the T-cells will help the T-cells to recognize and fight hematologic cancer. Once coding is successful, the new antigen-specific T-cells are replicated and infused into the patient’s bloodstream in order to attack the cancer cells.
STING agonist cGAMP enhances anti-tumor activity of CAR-NK cells against pancreatic cancer
Published in OncoImmunology, 2022
Yanyan Da, Yuxia Liu, Yuan Hu, Wenzeng Liu, Junpeng Ma, Nan Lu, Chengsheng Zhang, Cai Zhang
Chimeric antigen receptor (CAR), an artificially modified receptor protein, is composed of the extracellular domain of the single chain variable fragment (scFv) of the antibody, the hinge region, the transmembrane region, and an intracellular signal transduction domain.45 Compared to NK cells, CAR-modified NK cells can directly recognize and target specific antigens on the surface of tumor cells and exhibit enhanced cytotoxicity against tumor cells.46,47 In our previous work, we successfully established that CAR-NK-92 cells target MSLN, which were more effective in killing pancreatic cancer cells than NK-92 cells (Figure 5b,c). Because anti-MSLN CAR-NK-92 cells were derived from NK-92 cells, we did not repeat the cGAMP stimulation experiments in anti-MSLN CAR-NK-92 cells.
Hemophagocytic lymphohistiocytosis due to pembrolizumab therapy for adenocarcinoma of the lung
Published in Baylor University Medical Center Proceedings, 2021
James J. Doyle, James A. Hall, Kelsey Reely, Jyothi Dodlapati
Immunotherapy is designed to train the immune system to target tumor cells, but autoimmunity and other hyperinflammatory side effects need to be monitored.2 Its increasing use means these effects will become more prevalent.1 The immune checkpoint inhibitors that disrupt PD-1 to PD-L1 binding can cause HLH by their effects on leukocytes, both cytotoxic T cells as well as macrophages.3 The resulting cytokine storm that can occur as a side effect of these novel immunotherapies, as well as those targeting CTLA4 and chimeric antigen receptor T cells, can cause tissue injury or destruction, progressive organ failure, and even death.4,5 Histologically, this is seen as macrophages phagocytosing other hematologic components, though this is neither required for nor pathognomonic of a diagnosis of HLH.4,6
An overview of multiplexed analyses of CAR T-cell therapies: insights and potential
Published in Expert Review of Proteomics, 2021
Brittany Paige DePriest, Noah Vieira, Alan Bidgoli, Sophie Paczesny
The chimeric antigen receptor (CAR) is an engineered molecule that includes a single chain variable fragment (scFv) against a specific antigen combined with an extracellular hinge domain, a transmembrane domain, and an intracellular T-cell signaling domain. Constructed for use with the T-cell, CAR-T therapy works by recognizing the malignant cell and binding to the scFV target. The CAR-T-cell is then activated and targeted cell killing is initiated. The costimulatory domain drives signal amplification and functional T-cell expansion on repeat exposure to the tumor antigen [9,12,13]. Given the success of CAR-T therapy in hematologic malignancies, additional immune effector cells such as NK cells, invariant NK T-cells, γδ T-cells and even macrophages are being investigated for CAR engineering and therapeutic utility [8,14].