Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors. DLI represents a form of adoptive therapy used after hematopoietic stem cell transplant for its anti-tumor and anti-infectious properties. This article covers the current status of CAR-T cells and DLI research in the intensive care unit (ICU) patient, including the efficacy, toxicity, side effects and treatment.
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http://dx.doi.org/10.18632/oncotarget.24637 | DOI Listing |
BioDrugs
December 2024
Rheumatology Department, Strasbourg University Hospital, 1 Avenue Molière, 67000, Strasbourg, France.
Chimeric antigen receptor (CAR) T-cell therapy, initially successful in treating hematological malignancies, is emerging as a potential treatment for autoimmune diseases, including rheumatic conditions. CAR T cells, engineered to target and eliminate autoreactive B cells, offer a novel approach to managing diseases like systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myopathies, where B cells play a pivotal role in disease pathology. Early case reports have demonstrated promising results, with patients achieving significant disease remission, normalization of serological markers, and the ability to discontinue traditional immunosuppressive therapies, which supported the initiation of several clinical trials.
View Article and Find Full Text PDFJ Neurooncol
December 2024
Department of Neurosurgery, Warren Alpert Medical School of Brown University, 222 Richmond St, Providence, RI, 02903, USA.
Purpose: Chordoma, a rare malignancy of the axial skeleton and skull base, presents significant therapeutic challenges due to the high rates of tumor recurrence and resistance. While surgical resection and radiation therapy remain the gold standard of treatment, the lack of additional treatment options necessitates the exploration of novel therapies. Combinatorial therapies hold significant potential in shaping patient prognosis.
View Article and Find Full Text PDFSTAR Protoc
December 2024
Translational Research Unit, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway. Electronic address:
Chimeric antigen receptors (CARs) are synthetic molecules composed of an extracellular antigen-binding domain and an intracellular signaling domain, leading to tonic signaling and manufacturing challenges. We present a protocol for the expansion of tonic CARs by using a Food and Drug Administration (FDA)-approved kinase inhibitor, dasatinib. We report steps for T cell transduction with retrovirus, expansion and verification of CAR quality using flow cytometry, and killing assay.
View Article and Find Full Text PDFAnn Hematol
December 2024
Department of Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Miyagi, Japan.
Follicular lymphoma (FL) may undergo histological transformation (HT) into a more aggressive lymphoma. Although rituximab for B-cell non-Hodgkin lymphomas (B-NHL) has greatly improved the overall survival (OS) of patients with transformed FL (tFL), relapse after anthracycline-based chemoimmunotherapy has a poor prognosis. CD19-targeting chimeric antigen receptor-modified T-cell (CAR-T) therapy is a promising treatment for relapsed or refractory (r/r) large B-cell lymphoma (LBCL), including tFL.
View Article and Find Full Text PDFHere we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
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