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Tumor-specific T cells (TSTs) are essential components for the success of personalized tumor-infiltrating lymphocyte (TIL)-based adoptive cellular therapy (ACT). Therefore, the selection of a common biomarker for screening TSTs in different tumor types, followed by expansion to clinical number levels can generate the greatest therapeutic effect. However, studies on shared biomarkers for TSTs have not been realized yet. The present review summarizes the similarities and differences of a number of biomarkers for TSTs in several tumor types studied in the last 5 years, and the advantages of combining biomarkers. In addition, the review discusses the possible shortcomings of current biomarkers and highlights strategies to identify TSTs accurately using intercellular interactions. Finally, the development of TSTs in personalized TIL-based ACT for broader clinical applications is explored.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9702804 | PMC |
http://dx.doi.org/10.3389/fimmu.2022.1003626 | DOI Listing |
Br J Haematol
September 2025
Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Refractory cytomegalovirus (CMV) infection is a severe complication following umbilical cord blood transplantation (UCBT). Antiviral agents, the standard first-line therapy, are limited by toxicity and resistance without robust T-cell immunity. We evaluated third-party donor (TPD)-derived CMV-specific T cells (CMVSTs) as a treatment option.
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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