We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus-related acquired immunodeficiency syndrome and other infectious diseases.
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http://dx.doi.org/10.1126/science.1076514 | DOI Listing |
Cancer Res
December 2024
The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States.
Resistance of BRAF-mutant melanomas to targeted therapy arises from the ability of cells to enter a persister state, evade treatment with relative dormancy, and repopulate the tumor when reactivated. A better understanding of the temporal dynamics and specific pathways leading into and out of the persister state is needed to identify strategies to prevent treatment failure. Using spatial transcriptomics in patient-derived xenograft models, we captured clonal lineage evolution during treatment.
View Article and Find Full Text PDFLeukemia
December 2024
Department of Pathology, Hematopathology Section, University Hospital Schleswig-Holstein Campus, Kiel, Germany.
The Tumor Microenvironment (TME) in classical Hodgkin Lymphoma (HL) contains abundant immune cells and only few neoplastic Hodgkin and Reed-Sternberg cells (HRSC). We analyzed the T-cell receptor (TCR) repertoire to detect T-cell expansion in the TME and blood. In contrast to solid cancer tissue, T-cells in the TME of HL are highly polyclonal at first diagnosis and show only minor clonal expansion during anti-PD1 immune checkpoint blockade (ICB).
View Article and Find Full Text PDFElife
December 2024
Comprehensive Bone Marrow Failure Center, Children's Hospital of Philadelphia, Philadelphia, United States.
Hematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide range of hematopoietic precursors.
View Article and Find Full Text PDFbioRxiv
August 2024
Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
Stem Cell Reports
August 2024
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; The University of Melbourne, Melbourne, Victoria, Australia; School of Cellular and Molecular Medicine, University of Bristol, Bristol, England, UK. Electronic address:
It has been proposed that adult hematopoiesis is sustained by multipotent progenitors (MPPs) specified during embryogenesis. Adult-like hematopoietic stem cell (HSC) and MPP immunophenotypes are present in the fetus, but knowledge of their functional capacity is incomplete. We found that fetal MPP populations were functionally similar to adult cells, albeit with some differences in lymphoid output.
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