Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen that is frequently overexpressed in various carcinomas. We have developed chimeric antigen receptor (CAR) T cells specifically targeting EpCAM for the treatment of gastric cancer. This study sought to unravel the precise mechanisms by which tumors evade immune surveillance and develop resistance to CAR T cell therapy. Through a combination of whole-body CAR T cell imaging and single-cell multiomic analyses, we uncovered intricate interactions between tumors and tumor-infiltrating lymphocytes (TILs). In a gastric cancer model, tumor-infiltrating CD8 T cells exhibited both cytotoxic and exhausted phenotypes, while CD4 T cells were mainly regulatory T cells. A T cell receptor (TCR) clonal analysis provided evidence of CAR T cell proliferation and clonal expansion within resistant tumors, which was substantiated by whole-body CAR T cell imaging. Furthermore, single-cell transcriptomics showed that tumor cells in mice with refractory or relapsing outcomes were enriched for genes involved in major histocompatibility complex (MHC) and antigen presentation pathways, interferon- and interferon- responses, mitochondrial activities, and a set of genes (e.g., , , ) linked to tumor progression and unfavorable disease prognoses. This research highlights an approach that combines imaging and multiomic methodologies to concurrently characterize the evolution of tumors and the differentiation of CAR T cells.
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http://dx.doi.org/10.3390/cancers15235552 | DOI Listing |
Front Immunol
January 2025
Biotherapy Center & Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
We reported the pseudoprogression in an elderly patient with advanced gastric cancer after chimeric antigen receptor (CAR)-T cell therapy. The hepatic metastases enlarged 1 month after CAR-T cell infusion and then shrunk the next month as seen through computed tomography scanning. Based on a comprehensive evaluation that includes imaging, pathology, serum tumor markers, and clinical symptoms, we arrived at a diagnosis of pseudoprogression after CAR-T cell therapy, which has not been reported in previous studies.
View Article and Find Full Text PDFFront Bioeng Biotechnol
January 2025
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, Universitätsklinikum Erlangen, Erlangen, Germany.
Background: With the help of superparamagnetic iron oxide nanoparticles (SPIONs), cells can be magnetically directed so that they can be accumulated at target sites. This principle can be used to make monocytes magnetically steerable in order to improve tumor accumulation, e.g.
View Article and Find Full Text PDFFront Oncol
January 2025
Department of Hematology, Tianjin First Central Hospital, Tianjin, China.
Introduction: CD7 chimeric antigen receptor T-cell (CAR-T cell) therapy is an emerging method for treating hematological malignancies, and is another breakthrough in CAR-T cell therapy.
Methods: This study summarizes the currently published clinical research results on CD7 CAR-T cells and evaluates the safety and effectiveness of CD7 CAR-T cell therapy.
Results: Among the 13 studies included in this study, a total of 200 patients received CD7 CAR-T cell therapy, including 88 patients who received autologous CAR-T cells, 112 patients who received donor derived CAR-T cells.
Regen Ther
March 2025
Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Science, Tehran, Iran.
Gene therapy (GT) as a groundbreaking approach holds promise for treating many diseases including immune deficiencies and blood disorders. GT can benefit patients suffering from these diseases, especially those without matched donors or who are at risk after hematopoietic stem cell transplantation (HSCT). Due to all the advances in the field of GT, its main challenge is still gene delivery.
View Article and Find Full Text PDFJ Immunol Res
January 2025
Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made groundbreaking progress in the treatment of various cancer types, particularly hematological malignancies. In the meantime, various preclinical and clinical studies have extensively explored dual-target CAR-T therapies which can be designed to recognize two antigens simultaneously based on the immunophenotype of tumor cells. Compared with single-target CAR-T approach, dual-target CAR-T therapies demonstrate varying degrees of superior antitumor CAR effects, prevent antigen escape and relapse, reduce on-target off-tumor effects, and ensure durable responses in different types of cancer.
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