Objective: Experiments were designed to investigate a new concept aiming for induction of graft-vs-malignancy (GVM) effect prior to stem cell transplantation (SCT). Mismatched lymphocytes given pre-SCT will be followed by a selective elimination of alloreactive donor lymphocytes, thus avoiding lethal graft-vs-host disease (GVHD).
Methods: Recipient mice treated with sublethal total-body irradiation (TBI) received a single injection of allogeneic splenocytes, either naïve or rIL-2 activated (ADL), for induction of GVHD. To prevent lethal GVHD, cyclophosphamide (Cy) (200 mg/kg) or TBI (9 Gy) were given 4 days after cell inoculation. One day later, treated mice were rescued with syngeneic bone marrow cells.
Results: Both Cy and TBI significantly (p < 0.001) prevented GVHD in all recipients inoculated with either naïve cells or ADL and all recipients survived more than 250 days. Control mice not rescued with CY or TBI died of GVHD within 20 to 25 days. A significant proportion of recipients inoculated with 4T1 tumor cells, treated with ADL followed by TBI 9 Gy, survived more than 250 days disease-free in comparison with 22 days in untreated control mice (p <0.001).
Conclusions: Attempting to induce short, yet effective, GVM effects before rather than after SCT, thus avoiding lethal GVHD, may represent an innovative approach for more effective yet safer use of SCT for tumor immunotherapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.exphem.2004.04.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CD47;Rag2;IL-2rγ triple knock-out mice pre-conditioning with busulfan could be a novel platform for generating hematopoietic stem cells engrafted humanized mice.
Front Immunol
August 2024
Convergence Medicine Research Center, Asan Medical Center, Seoul, Republic of Korea.
Introduction: Humanized mouse models to recapitulate human biological systems still have limitations, such as the onset of lethal graft-versus-host disease (GvHD), a variable success rate, and the low accessibility of total body irradiation (TBI). Recently, mice modified with the CD47-SIRPA axis have been studied to improve humanized mouse models. However, such trials have been rarely applied in NOD mice.
View Article and Find Full Text PDFTransplantation in adult patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: yes or no?
Blood
November 2024
Department of General Practice, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Article Synopsis
- Hemophagocytic lymphohistiocytosis (HLH) is a serious immune system disorder, with the most common form in adults being Epstein-Barr virus (EBV)-associated HLH (EBV-HLH), which can lead to severe outcomes depending on the type of immune cells affected.
- In a study of 356 adult patients with EBV-HLH, those who underwent allogeneic hematopoietic stem cell transplantation (HSCT) had a significantly better 5-year survival rate (48.7%) compared to those who did not receive transplantation (16.2%).
- Factors like EBV-DNA levels, remission status, and the presence of graft-versus-host disease influenced survival
Fecal Microbiota Transfer in Acute Graft-versus-Host Disease following Allogeneic Stem Cell Transplantation.
Visc Med
March 2024
Department of Internal Medicine III (Haematology/Oncology), University Hospital Regensburg, Regensburg, Germany.
Background: Acute graft-versus-host disease (GvHD) is a major and sometimes lethal complication following allogeneic stem cell transplantation (aSCT). In the last 10 years, a massive loss of microbiota diversity with suppression of commensal bacteria and their protective metabolites has been identified as a major risk factor of GvHD.
Summary: Since 2018, several studies have been published showing some efficacy of fecal microbiota transfer (FMT) in aSCT patients.
Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation.
Immunity
July 2024
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address:
Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs.
View Article and Find Full Text PDFCD8 T cell-mediated rejection of allogenic human-induced pluripotent stem cell-derived cardiomyocyte sheets in human PBMC-transferred NOG MHC double knockout mice.
J Heart Lung Transplant
August 2024
Center for Immune Therapeutics and Diagnosis, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address:
Background: Transplantation of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) has emerged as a promising therapy to treat end-stage heart failure. However, the immunogenicity of hiPS-CMs in transplanted patients has not been fully elucidated. Thus, in vivo models are required to estimate immune responses against hiPS-CMs in transplant recipients.
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!