ArticleThe Journal of clinical investigation2021
Antibody-drug conjugates plus Janus kinase inhibitors enable MHC-mismatched allogeneic hematopoietic stem cell transplantation.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Immune reset: what do we learn from bone marrow transplantation.Medical review (2021) · 2026Review
- Improved conditioning for hematopoietic chimerism induces islet tolerance to cure diabetes.JCI insight · 2026Article
- Clonal dynamics, tolerance, and adverse events after CD45-ADC-conditioned autologous HSPC transplantation in macaques.Blood advances · 2026Article
- Preventing graft re-JAK-tion: safer transplant conditioning enables murine islet allograft tolerance and diabetes reversal.The Journal of clinical investigation · 2026Article
- Radioimmunotherapy as a targeted strategy of reduced-intensity conditioning for allogeneic transplantation in leukemia.Frontiers in oncology · 2026Review
- Streptavidin-drug conjugates streamline optimization of antibody-based hematopoietic stem cell transplant conditioning.Blood immunology & cellular therapy · 2025Article
- Review
- Article
- A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice.Nature communications · 2025Article
- Improved safety of chimeric antigen receptor T cells indirectly targeting antigens via switchable adapters.Nature communications · 2024Article
- Conditioning with anti-CD47 and anti-CD117 plus JAK inhibition enables toxic payload-free allogeneic transplantation.Blood advances · 2024Article
- Article
- Major breakthroughs in hematopoietic stem cell transplantation and future challenges in clinical implementation.The Journal of clinical investigation · 2024Article
- cMPL-Based Purification and Depletion of Human Hematopoietic Stem Cells: Implications for Pre-Transplant Conditioning.bioRxiv : the preprint server for biology · 2024Article
- Review
- Curative islet and hematopoietic cell transplantation in diabetic mice without toxic bone marrow conditioning.Cell reports · 2022Article
- Across the Myeloablative Spectrum: Hematopoietic Cell Transplant Conditioning Regimens for Pediatric Patients with Sickle Cell Disease.Journal of clinical medicine · 2022Review
- Worked to the bone: antibody-based conditioning as the future of transplant biology.Journal of hematology & oncology · 2022Review
- Where do we stand with radioimmunotherapy for acute myeloid leukemia?Expert opinion on biological therapy · 2022Article
- The Hematology of Tomorrow Is Here-Preclinical Models Are Not: Cell Therapy for Hematological Malignancies.Cancers · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Despite the curative potential of hematopoietic stem cell transplantation (HSCT), conditioning-associated toxicities preclude broader clinical application. Antibody-drug conjugates (ADCs) provide an attractive approach to HSCT conditioning that minimizes toxicity while retaining efficacy. Initial studies of ADC conditioning have largely focused on syngeneic HSCT. However, to treat acute leukemias or induce tolerance for solid organ transplantation, this approach must be expanded to allogeneic HSCT (allo-HSCT). Using murine allo-HSCT models, we show that pharmacologic Janus kinase 1/2 (JAK1/2) inhibition combined with CD45- or cKit-targeted ADCs enables robust multilineage alloengraftment. Strikingly, myeloid lineage donor chimerism exceeding 99% was achievable in fully MHC-mismatched HSCT using this approach. Mechanistic studies using the JAK1/2 inhibitor baricitinib revealed marked impairment of T and NK cell survival, proliferation, and effector function. NK cells were exquisitely sensitive to JAK1/2 inhibition due to interference with IL-15 signaling. Unlike irradiated mice, ADC-conditioned mice did not develop pathogenic graft-versus-host alloreactivity when challenged with mismatched T cells. Finally, the combination of ADCs and baricitinib balanced graft-versus-host disease and graft-versus-leukemia responses in delayed donor lymphocyte infusion models. Our allo-HSCT conditioning strategy exemplifies the promise of immunotherapy to improve the safety of HSCT for treating hematologic diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.