AI Article Synopsis
- CAR T-cell therapy can lead to significant toxicities, including a severe form resembling haemophagocytic lymphohistiocytosis (carHLH), which affects 14.8% of pediatric and young adult patients.
- The risk of developing carHLH is higher in patients with a significant disease burden, necessitating careful monitoring and prompt diagnosis.
- Patients with carHLH experience lower response rates and overall survival outcomes compared to those without it, highlighting the need for effective management strategies.
Article Abstract
Chimeric antigen receptor T-cell (CAR T-cell) therapy is associated with significant toxicities secondary to immune activation, including a rare but increasingly recognised severe toxicity resembling haemophagocytic lymphohistiocytosis (carHLH). We report the development of carHLH in 14·8% of paediatric patients and young adults treated with CD19-specific CAR T-cell therapy with carHLH, occurring most commonly in those with high disease burden. The diagnosis and treatment of carHLH required a high index of suspicion and included multidrug immunomodulation with variable response to therapies. Compared to patients without carHLH, patients with carHLH had both reduced response to CAR T-cell therapy (P-value = 0·018) and overall survival (P-value = < 0·0001).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756350 | PMC |
| http://dx.doi.org/10.1111/bjh.17662 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bioconjugation of Synthetic Peptides onto Universal Chimeric Antigen Receptor T Cells for Targeted Cancer Immunotherapies.
ACS Nano
January 2025
Department of Bioengineering, University of Washington, Seattle, Washington 98195-5061, United States.
The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting.
View Article and Find Full Text PDFIntegrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody response.
Blood
January 2025
University of Chicago, Chicago, Illinois, United States.
Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.
View Article and Find Full Text PDFEmerging Frontiers in Colorectal Cancer Therapy: From Targeted Molecules to Immunomodulatory Breakthroughs and Cell-Based Approaches.
Dig Dis Sci
January 2025
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Yeman St, Chamran Expressway, P.O. Box 19857-17413, Tehran, Iran.
Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes.
View Article and Find Full Text PDFUnlabelled: ICANS is a common form of neurological immunotoxicity from CAR T-cell therapy (CAR-T). While high tumor burden, product type and cell dose are established risk factors, there are many unknowns. Our objective was to characterize novel neurological and non-neurological risk factors for the development of ICANS in subjects who received CAR-T.
View Article and Find Full Text PDFDevelopment of chimeric antigen receptor T cells targeting cancer-expressing podocalyxin.
Regen Ther
March 2025
Department of Cancer Immunotherapy and Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Chimeric Antigen Receptor (CAR)-T cell therapy has revolutionized the treatment of CD19-positive B-cell malignancies. However, the field is rapidly evolving to target other antigens, such as podocalyxin (PODXL), a transmembrane protein implicated in tumor progression and poor prognosis in various cancers. This study explores the potential of PODXL-targeted CAR-T cells, utilizing a cancer-specific monoclonal antibody (CasMab) technique to enhance the specificity and safety of CAR-T cell therapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!