Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Pseudo-progression and flare-up phenomena constitute a novel diagnostic challenge in the follow-up of patients treated with immune-oncology drugs. We present a case study on pulmonary flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T-cell therapy, and used single-cell RNA-seq (scRNA-seq) to identify a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon. By integrating datasets of various lung pathological conditions, we revealed transcriptomic similarities between post CAR T pulmonary lesions and sarcoidosis. Furthermore, we explored a noninvasive PET based diagnostic approach and showed that tracers binding to CXCR4 complement FDG PET imaging in this setting, allowing discrimination between immune-mediated changes and true relapse after CAR T-cell treatment. In conclusion, our study highlights a Th17.1 driven autoimmune phenomenon after CAR T, which may be misinterpreted as disease relapse, and that imaging with multiple PET tracers and scRNA-seq could help in this diagnostic dilemma.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9888347 | PMC |
| http://dx.doi.org/10.1038/s41375-023-01824-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sequential intrathoracic injection and intravenous infusion of BCMA CAR-T cells in a patient with relapsed/refractory primary plasma cell leukemia.
Int J Hematol
September 2025
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China.
Patients with primary plasma cell leukemia (pPCL), particularly those with extramedullary disease (EMD), face a poor prognosis even with chimeric antigen receptor (CAR)-T cell therapy. This case report describes a patient with relapsed/refractory pPCL and life-threatening malignant pleural effusion (PE) treated with intrapleural CAR-T cells targeting B-cell maturation antigens. CAR-T cell expansion within the PE was observed, along with a rapid reduction in leukemia cell count and PE volume.
View Article and Find Full Text PDFNanotechnology for CAR T cells and tumour-infiltrating lymphocyte therapies.
Nat Nanotechnol
September 2025
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Adoptive T-cell therapies, and particularly CAR T cells and tumour-infiltrating lymphocytes, have transformed cancer treatment by selectively targeting malignant cells. Despite their clinical success, these therapies face substantial challenges, including costly manufacturing processes and tumour-imposed barriers that limit efficacy. Advances in understanding the nanoscale mechanisms governing T-cell activation and the role of the tumour microenvironment in restricting T-cell responses have driven the development of nanotechnology-based strategies that integrate key chemical and physical cues.
View Article and Find Full Text PDFModulating the PPARγ pathway upregulates NECTIN4 and enhances chimeric antigen receptor (CAR) T cell therapy in bladder cancer.
Nat Commun
September 2025
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
With the approval of the antibody-drug conjugate enfortumab vedotin (EV), NECTIN4 has emerged as a bona fide therapeutic target in urothelial carcinoma (UC). Here, we report the development of a NECTIN4-directed chimeric antigen receptor (CAR) T cell, which exhibits reactivity across cells expressing a range of endogenous NECTIN4, with enhanced activity in high expressors. We demonstrate that the PPARγ pathway, critical for luminal differentiation, transcriptionally controls NECTIN4, and that the PPARγ agonist rosiglitazone primes and augments NECTIN4 expression, thereby increasing sensitivity to NECTIN4-CAR T cell-mediated killing.
View Article and Find Full Text PDFTandem CAR-T cells targeting mesothelin and MUC16 overcome tumor heterogeneity by targeting one antigen at a time.
J Immunother Cancer
September 2025
Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA
Background: Tumor heterogeneity and antigen escape are mechanisms of resistance to chimeric antigen receptor (CAR)-T cell therapy, especially in solid tumors. Targeting multiple antigens with a unique CAR construct could be a strategy for a better tumor control than monospecific CAR-T cells on heterogeneous models. To overcome tumor heterogeneity, we targeted mesothelin (meso) and Mucin 16 (MUC16), two antigens commonly expressed in solid tumors, using a tandem CAR design.
View Article and Find Full Text PDFComparative efficacy and safety of PSCA CAR-engineered Vδ1 γδ T cells for immunotherapy of pancreatic cancer.
J Immunother Cancer
September 2025
Division of Hematology & Oncology, Department of Medicine, School of Medicine, University of California, Irvine, California, USA
Background: γδ T cells possess unique immunological features including tissue tropism, major histocompatibility complex-independent antigen recognition, and hybrid T/natural killer cell properties that make them promising candidates for cancer immunotherapy. However, the therapeutic potential of Vδ1 γδ T cells, particularly when engineered with chimeric antigen receptors (CARs), remains underexplored in solid tumors such as pancreatic cancer (PC), largely due to their low abundance in peripheral blood and challenges in ex vivo expansion. This study aims to directly compare the preclinical safety and efficacy among CAR-engineered Vδ1 γδ T cells, Vδ2 γδ T cells, and conventional αβ T cells.
View Article and Find Full Text PDF