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Background: Patients receiving hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR T-cell) therapy are immunocompromised and at high risk of viral infection, including SAR2-CoV-2 infection. However, the effectiveness and safety of COVID-19 vaccines in these recipients is not well characterized. The present meta-analysis evaluated the serologic response and safety of COVID-19 vaccines in these population.
Methods: Literature databases (MEDLINE, EMBASE, Web of Science, MedRvix and BioRvix) were searched for original studies with serologic response post COVID-19 vaccination in HSCT or CAR T-cell recipients published until July 14, 2022. The analysis included 27 observational studies with a total of 2899 patients receiving allogeneic HSCT (2506), autologous HSCT (286) or CAR T-cell therapy (107), and 683 healthy participants with serologic response data. Random effects models were used to pool the rate of serologic response to COVID-19 vaccination in HSCT or CAR T-cell recipients and odds ratio comparing with healthy controls.
Results: The pooled seropositivity rates in HSCT and CAR T-cell recipients were 0.624 [0.506-0.729] for one dose, 0.745 [0.712-0.776] for two doses. The rates were significantly lower than those in healthy controls (nearly 100%). In subgroup analysis, CAR T-cell recipients exhibited an even lower seroconversion rate (one dose: 0.204 [0.094-0.386]; two doses: 0.277 [0.190-0.386]) than HSCT counterparts (one dose: 0.779 [0.666-0.862]; two doses: 0.793 [0.762-0.821]). The rates were comparable between autologous and allogeneic HSCT recipients. Other possible impact factors related to seropositivity were time interval between therapy and vaccination, use of immunosuppressive drugs and immune cell counts. Most vaccine-related adverse effects were mild and resolvable, comparable to general population.
Conclusions: This analysis revealed a diminished response to COVID-19 vaccines in HSCT or CAR T-cell recipients. Our findings may inform regular COVID-19 vaccination at appropriate intervals after HSCT or CAR T-cell therapy.
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http://dx.doi.org/10.1186/s40164-022-00299-6 | DOI Listing |
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 PDFNat 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 PDFNat 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 PDFJ 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 PDFJ 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.
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