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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.
Selection of Endpoints
Published in Susan Halabi, Stefan Michiels, Textbook of Clinical Trials in Oncology, 2019
Katherine S. Panageas, Andrea Knezevic
Clinical trials have enabled new and promising treatments, resulting in medical breakthroughs in oncology. The development of both targeted or molecular therapy that interferes with specific molecular targets and immunotherapy that targets the immune system has contributed to the recent expansion of clinical trials in oncology. In 2013, Science declared cancer immunotherapy to be the breakthrough of the year based on the positive results of clinical trials of antibodies that block negative regulators of T-cell function, and the development of genetically modified T cells (chimeric antigen receptor T-cell therapy) [8]. Evaluation of novel agents typically progresses through a three-phase system of clinical trials (phase I, II, and III). A new treatment that is successful in one phase will continue to be tested in subsequent phases.
The Cardiovascular System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Calvert Louden, David Brott, Chidozie J. Amuzie, Bindu Bennet, Ronnie Chamanza
Infusion reactions are a group of biopharmaceutical exposure-related hemodynamic observations that are often seen within hours of the initial dose of a biotherapeutic in humans and animals, meaning that pre-existing ADA are not required for these observations. In chimeric antigen receptor T-cell (CAR-T), these observations may not occur immediately after the first dose but are generally associated with critical expansion of the T-cell population at/or near the time of first dose. Significant hemodynamic changes were seen in a first dose reaction observed in the Phase 1 clinical trial of a humanized anti-CD28 (TGN 1412) in healthy volunteers. All volunteers had marked elevation of T-cell activation-related cytokines such as interleukin-2 and interferon-γ, but the most severe cases also had sustained elevation of tumor necrosis factor-α, interleukins 1, 4, and 6 during the clinical syndrome now named “cytokine release syndrome” (Suntharalingam et al. 2006). The TGN 1412 patients also had a range of clinical chemistry findings that were interpreted to represent multi-organ failure. However, due to the absence of histopathology samples from these patients the morphologic alteration in the vascular/perivascular system of TGN 1412 could not be ascertained. More recently, diverse immunostimulatory and/or immunooncology agents such as the CAR-T Tisagenlecleucel (Kymriah®) or CD19 Bi-specific T-cell engager Blinatumomab (Blincyto®) have been associated with elevations of the same spectrum of cytokines that were seen in TGN 1412, as well as decreases in blood pressure with increased HR (EMA 2015; FDA 2017).
Immunotherapy and next-generation sequencing guided therapy for precision oncology: what have we learnt and what does the future hold?
Published in Expert Review of Precision Medicine and Drug Development, 2018
Roman Groisberg, Hossein Maymani, Vivek Subbiah
Next-generation sequencing (NGS) is able to quickly, reliably, and affordably detect actionable alterations for targeted therapy in cancers.Neoantigens are highly immunogenic protein fragments and are the critical step in immune surveillance.NGS and novel computational algorithms are being used to identify neoantigens.NGS has the advantage of speed and cost when compared to older cDNA based neoantigen identification.The identification of neoantigens is used to construct cell transfer therapy such as tumor infiltrating lymphocytes (TILs).Chimeric antigen receptor T-cell therapy (CAR-T) is proving extremely successful in leukemias and lymphomas, but has not yet made in-roads in solid tumors because of a lack of consistent antigen target.NGS based identification of neoantigens may make personalized CAR-Ts or cancer vaccines possible for individual solid tumor patients.The combination of NGS and immunotherapy promises to bring truly personalized cancer care to an increasing number of cancer patients.
BCMA-targeted therapies for multiple myeloma: strategies to maximize efficacy and minimize adverse events
Published in Expert Review of Hematology, 2022
Edmund Watson, Faouzi Djebbari, Alexandros Rampotas, Karthik Ramasamy
Chimeric antigen receptor T-cell (CAR T) therapy combines antibody specificity with T-cell anti-tumor activity. Patient-derived T-cells obtained through leukapheresis are engineered to express a chimeric receptor that carries an antigen-recognition domain most often a single chain of variable fragments (scFv) fused with CD3 and a co-stimulatory molecule (usually 4–1BB or CD28) [43]; see Figure 2. Engagement of the CAR with its target triggers T cell activation and proliferation in a non- MHC-restricted fashion that does not require professional antigen presenting cells, thus bypassing some mechanisms by which cancers resist therapy.
CAR-T cell therapy and infection: a review
Published in Expert Review of Anti-infective Therapy, 2021
Olivia Bupha-Intr, Gabrielle Haeusler, Lynette Chee, Karin Thursky, Monica Slavin, Benjamin Teh
Chimeric antigen receptor T-cell therapy (CAR-T cell therapy) is a novel adoptive immunotherapy that represents a dramatic advance in cancer therapy. T-lymphocytes are genetically engineered using a viral vector carrying a chimeric antigen receptor (CAR). The CAR encodes for an extracellular domain for tumor antigen recognition (such as CD19 to recognize B cells) which is linked to an intracellular signaling domain that mediates T-cell activation. These modified T-lymphocytes are then infused into the patient to target and eliminate cancer cells by utilizing the patient’s immune system.