Natural killer (NK) cell alloreactivity resulting from killer immunoglobulin-like receptor (KIR) ligand incompatibility improves outcomes in patients receiving extensively T-cell-depleted bone marrow (BM) grafts. Patients with KIR ligand incompatibility are at risk for donor T-cell alloreactivity. We investigated the relative significance of NK-cell and T-cell alloreactivity in 105 paediatric patients who received a minimally T-cell-depleted human leucocyte antigen-non-identical BM transplantation. Donor NK-cell incompatibility did not improve patient outcome [engraftment, graft-versus-host disease (GVHD), relapse or overall survival]. In contrast, donor T-cell incompatibility was a risk factor for acute GVHD, chronic GVHD and death. Thus, T-cell alloreactivity dominated that of NK cells in minimally T-cell-depleted grafts.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1046/j.1365-2141.2003.04604.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Depletion of alloreactive B cells by drug-resistant chimeric alloantigen receptor T cells to prevent transplant rejection.
Mol Ther
January 2025
Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, 30625 Hannover, NI, Germany. Electronic address:
Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.
View Article and Find Full Text PDFCD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.
Cell Rep Med
January 2025
Bone Marrow Transplantation Center of the First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 311121, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou 310058, China. Electronic address:
Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).
View Article and Find Full Text PDFLong-term remission following CAR-T therapy in a patient with transformed follicular lymphoma relapse after allogeneic stem cell transplantation.
Ann Hematol
December 2024
Department of Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Miyagi, Japan.
Follicular lymphoma (FL) may undergo histological transformation (HT) into a more aggressive lymphoma. Although rituximab for B-cell non-Hodgkin lymphomas (B-NHL) has greatly improved the overall survival (OS) of patients with transformed FL (tFL), relapse after anthracycline-based chemoimmunotherapy has a poor prognosis. CD19-targeting chimeric antigen receptor-modified T-cell (CAR-T) therapy is a promising treatment for relapsed or refractory (r/r) large B-cell lymphoma (LBCL), including tFL.
View Article and Find Full Text PDFChronic Graft-versus-host Disease: Immune Insights, Therapeutic Advances, and Parallels for Solid Organ Transplantation.
Transplantation
December 2024
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.
Chronic graft-versus-host disease remains a frequent and morbid outcome of allogeneic hematopoietic cell transplantation, in which the donor-derived immune system attacks healthy recipient tissue. Preceding tissue damage mediated by chemoradiotherapy and alloreactive T cells compromise central and peripheral tolerance mechanisms, leading to aberrant donor T cell and germinal center B cell differentiation, culminating in pathogenic macrophage infiltration and differentiation in a target tissue, with ensuant fibrosis. This process results in a heterogeneous clinical syndrome with significant morbidity and mortality, frequently requiring prolonged therapy.
View Article and Find Full Text PDFGenetically modified, induced pluripotent stem cells (iPSCs) offer a promising allogeneic source for the generation of functionally enhanced, chimeric antigen receptor (CAR) T cells. However, the signaling of CARs during early T cell development and the removal of the endogenous T cell receptor required to prevent alloreactivity pose significant challenges to the production of mature conventional CAR T cells from iPSCs. Here, we show that TCR-null, CD8αβ CAR T cells can be efficiently generated from iPSCs by engineering stage-specific onset of CAR expression and signaling to both permit conventional T cell development and to induce efficient positive selection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!