A Novel Targeted Approach to Achieve Immune System Reset: CD45-Targeted Antibody Drug Conjugates Enable Autologous HSCT and Ameliorate Disease in Preclinical Autoimmune Disease Models

Resetting the immune system through autologous hematopoietic stem cell transplant (autoHSCT) is a highly effective treatment in patients with autoimmune diseases (AID). AutoHSCT achieved long-term remission in patients with relapsed refractory and secondary progressive multiple sclerosis (Muraro 2017), superior to their previous standard of care (Burt 2019). AutoHSCT in scleroderma patients achieved superior outcomes in two randomized studies (Tyndall 2014, Sullivan 2018). These impressive results are achieved by both eradication of autoreactive immune effector cells and re-establishment of a self-tolerant immune system, i.e., immune system reset.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 469 Source Type: research

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Purpose of review Autologous hematopoietic stem cell transplantation (HSCT) is a promising therapeutic modality for severe autoimmune diseases. In this review, we will outline the immunological mechanisms and the clinical evidence and experiences for therapeutic HSCT in autoimmune diseases, with particular focus on systemic sclerosis and multiple sclerosis. Recent findings Approximately 3000 patients with autoimmune diseases worldwide have been treated with HSCT. HSCT in systemic sclerosis has been shown in three randomized controlled trials to be associated with significant long-term event-free survival despite some ...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by David Rizzieri Source Type: research
Qiancheng Deng1, Yangyang Luo1,2, Christopher Chang3, Haijing Wu1, Yan Ding4* and Rong Xiao1* 1Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China 2Department of Dermatology, Hunan Children's Hospital, Changsha, China 3Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States 4Department of Dermatology, Hainan Provincial Dermatology Disease Hospital, Haikou, China Autoimmune diseases are usually complex and multifactorial, characterized by aberrant produc...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsThis first SFGM-TC retrospective report shows long-term benefit of AHSCT in AD patients with acceptable toxicity.
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Abstract Haematopoietic stem cell transplantation was proposed as a treatment strategy just over 60 years ago. Owing to great advances in the field, haematopoietic stem cell transplantation has become an established method for the treatment of many haemato-oncological, immunological and hereditary conditions with the potential of cure. The number of haematopoietic stem cell transplants performed worldwide reached one million by 2012. This review provides an overview of autologous and allogeneic haematopoietic stem cell transplantation including disease indications, the individual steps of the procedure and outcome...
Source: British Journal of Hospital Medicine - Category: Internal Medicine Authors: Tags: Br J Hosp Med (Lond) Source Type: research
CONCLUSIONThis study confirms that the morbidity and mortality of ASCT for patients with autoimmune disease is similar to that for other patient groups undergoing ASCT. Patient selection should take this into consideration.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 731. Clinical Autologous Transplantation: Results: Poster III Source Type: research
Purpose of review To summarize the current clinical experience in the use of autologous hematopoietic stem cell transplantation (HSCT) in autoimmune disease and to explore the concept of durable remission induction and tissue de-remodeling via restoration of normal niche function and “immune reset." Recent findings Controlled clinical trials in systemic sclerosis, multiple sclerosis, and Crohn's disease as well as extensive uncontrolled trial and registry data have established the unique role of HSCT in selected cases. Although HSCT for multiple sclerosis and systemic sclerosis has recently entered several ...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research
Publication date: Available online 29 May 2017 Source:Autoimmunity Reviews Author(s): Margit Zeher, Gábor Papp, Britt Nakken, Peter Szodoray Autoimmune diseases are characterized by the development of autoreactive T- and B-cells targeting self-antigens, which eventually can result in chronic and persistent organ damage. The autologous hematopoietic stem cell transplantation (AHSCT) opened new avenues in the treatment of patients with severe, treatment-resistant autoimmune diseases. This paper reviews the immune-regulatory mechanisms behind AHSCT, and also summarizes the experiences of clinical practice related to t...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Abstract Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin co...
Source: Presse Medicale - Category: Journals (General) Authors: Tags: Presse Med Source Type: research
Abstract For patients with severe and refractory autoimmune diseases, high‐dose chemotherapy and autologous hematopoietic stem cell transplantation has been established as a considerable therapeutic option in recent years. In this retrospective single‐center analysis, we assessed the feasibility and efficacy of peripheral blood stem cells (PBSC) mobilization and collection in 35 patients with refractory autoimmune disease (AID). The mobilization data of 15 patients with systemic sclerosis (SSc), 11 patients with multiple sclerosis (MS), and 9 patients with other AID were analyzed. Stem cell mobilization with cyclophosp...
Source: European Journal of Haematology - Category: Hematology Authors: Tags: Original Article Source Type: research
Abstract Autologous stem cell transplantation (HSCT) has been used for over thirty years for malignant haematological diseases such as myeloma and lymphoma with considerable success. More recently this procedure has been adopted as a form of high dose immunosuppression in selected patients with auto‐immune diseases that are resistant to conventional therapies. Animal models have previously outlined the rationale and validity of HSCT in patients with these non‐malignant, but in many cases, life threatening conditions. Recent data has demonstrated that deletion of putative auto‐reactive immune clones with reconstitutio...
Source: Internal Medicine Journal - Category: Internal Medicine Authors: Tags: Review Source Type: research
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