- Home
- Knowledge Base
- References
In utero HSC transplantation for sickle cell disease: A potential therapeutic approach that overcomes complications of current therapies
Babatunde OO, Bibby MG, Atala A, Almeida-Porada G, Porada CD (2026) In utero HSC transplantation for sickle cell disease: A potential therapeutic approach that overcomes complications of current therapies. Prenat Diagn doi: 10.1002/pd.70142 PMID: 41936060
Objective: To examine current evidence and recent advances for treatment of sickle cell disease (SCD).
Summary: Biotinylated anti‐c‐kit/CD117 mAb coupled to a streptavidin‐conjugated saporin has been used to selectively deplete host HSC while preserving the host’s immune system. A single intravenous dose of the anti‐CD45‐saporin ADC enabled > 90% donor (congenic) hematopoietic engraftment and full correction of the SCD phenotype.
Related Products: Anti-CD117-SAP (Cat. #IT-83), Streptavidin-ZAP (Cat. #IT-27), Anti-CD45.2-SAP (Cat. #IT-91)
Streptavidin-drug conjugates streamline optimization of antibody-based hematopoietic stem cell transplant conditioning
Yelamali AR, Chendamarai E, Ritchey JK, Rettig MP, DiPersio JF, Persaud SP (2025) Streptavidin-drug conjugates streamline optimization of antibody-based hematopoietic stem cell transplant conditioning. Blood ICT 1(3):100012. doi: 10.1016/j.bict.2025.100012 PMID: 41574174
Objective: To develop and validate a modular streptavidin based antibody drug conjugate platform for optimizing antibody mediated hematopoietic stem cell transplant conditioning.
Summary: The authors demonstrate that a streptavidin drug conjugate system enables rapid comparison of antibody payload combinations for hematopoietic stem cell depletion and leukemia targeting. The study builds on prior work using CD45 targeted immunotoxins to achieve effective hematopoietic niche depletion in murine HSCT models.
Usage: This study references earlier conditioning experiments that utilized Streptavidin-ZAP (IT-27) in combination with biotinylated CD45 antibodies to selectively deplete hematopoietic stem cells in murine HSCT models, typically administered as a single intravenous dose of approximately 75 µg per mouse.
Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD45.2-SAP (Cat. #IT-91)
A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice
Konturek-Ciesla A, Zhang Q, Kharazi S, Bryder D (2025) A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice. Nat Commun 16(1):5129. doi: 10.1038/s41467-025-60464-3 PMID: 40456713
Objective: Application of Hematopoietic stem cell (HSC) transplantation leads to treatment toxicity. Therefore, authors employed a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated HSC depletion to improve hematopoietic output and ameliorate age-compromised lymphopoiesis.
Summary: Authors demonstrate that young HSCs, once effectively engrafted in aged hosts, improve hematopoietic output and ameliorate age-compromised lymphopoiesis. This culminated in a strategy that robustly mitigates disease progression in a genetic model of myelodysplastic syndrome. These results suggest that non-genotoxic HSC transplantation could fundamentally change the clinical management of age-associated hematological disorders, offering a prophylactic tool to delay or even prevent their onset in elderly patients.
Usage: CD45-SAP (3 mg/kg) was administered to young (2 months) and aged (16 months) C57BL/6-CD45.2 mice
Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)
Approaches for studying neuroimmune interactions in Alzheimer’s disease
Lin CCJ, Tian Y, Tanzi RE, Jorfi M (2024) Approaches for studying neuroimmune interactions in Alzheimer’s disease. Trends Immunol S1471-4906(24)00248-5. doi: 10.1016/j.it.2024.10.002 PMID: 39537528
Objective: To examine cutting-edge strategies – encompassing animal and cellular models – used to investigate the roles of peripheral immune cells in AD.
Summary: Recent studies using rodent models and innovative human-based cellular systems are beginning to shed light on how peripheral immune cells infiltrate the brain and modulate disease progression.
Usage: Strategies for bone marrow depletion using anti-CD45 or anti-CD117 antibodies conjugated with the ribosome-inactivating protein saporin have been used.
Related Products: Anti-CD117-SAP (Cat. #IT-83), Anti-CD45.2-SAP (Cat. #IT-91)
See Also:
- Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
- Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.
Correction of osteopetrosis in the neonate oc/oc murine model after lentiviral vector gene therapy and non-genotoxic conditioning
Penna S, Zecchillo A, Di Verniere M, Fontana E, Iannello V, Palagano E, Mantero S, Cappelleri A, Rizzoli E, Santi L, Crisafulli L, Filibian M, Forlino A, Basso-Ricci L, Scala S, Scanziani E, Schinke T, Ficara F, Sobacchi C, Villa A, Capo V (2024) Correction of osteopetrosis in the neonate oc/oc murine model after lentiviral vector gene therapy and non-genotoxic conditioning. Front Endocrinol (Lausanne) 15:1450349. doi: 10.3389/fendo.2024.1450349 PMID: 39314524
Objective: To investigate whether gene therapy (GT) could minimize the immune-mediated complications of allogeneic hematopoietic stem cell transplantation (HSCT) and offer a prompt treatment.
Summary: Authors showed that lentiviral vector GT can revert the osteopetrotic bone phenotype, allowing long-term survival and reducing extramedullary haematopoiesis and that plerixafor-induced mobilization can further increase the high number of HSPCs circulating in peripheral blood, facilitating the collection of adequate numbers of cells for therapeutic purposes. Pre-transplant non-genotoxic conditioning allowed the stable engraftment of HSPCs, albeit at lower level than conventional total body irradiation, and led to long-term survival and correction of bone phenotype, in the absence of acute toxicity.
Usage: Recipient oc/oc mice were conditioned by CD45-SAP injections or total body irradiation (IRR)
Related Products: Anti-CD45.2-SAP (Cat. #IT-91)
A non-invasive stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice
Bryder D, Konturk-Ciesla A, Zhang Q, Kharazi S (2024) A non-invasive stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice. Research Square doi: 10.21203/rs.3.rs-4528815/v1
Objective: To develop a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated Hematopoietic stem cell.
Summary: Authors demonstrate that young HSCs, once transplanted, survive and thrive in aged hosts, dramatically improving hematopoietic output and ameliorating age-compromised lymphopoiesis.
Usage: Intravenous injection of CD45-SAP (3 mg/kg, IT-91). Biotinylated anti-CD45.2 antibodies were mixed with streptavidin-saporin conjugate at a 1:1 molar ratio (IT-27).
Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)
Engineering an antibody-discernible and functional CD45 variant on hematopoietic stem and progenitor cells via base editing
Garaudé S (2024) Engineering an antibody-discernible and functional CD45 variant on hematopoietic stem and progenitor cells via base editing. Univ Basel Thesis.
Objective: To develop a system for a cell surface marker present on all hematopoietic cell to deplete malignant cells. Authors screened CD45’s extracellular domain regions with base editors and generated multiple CD45 protein variants altering the binding of antibodies.
Summary: Authors selected the CD45 K352E/G variant profile and improved its base editing rate as it showcased loss of binding of a unique anti-CD45 antibody while still maintaining the surface marker’s expression, stability, and function in human hematopoietic stem and progenitor cells (HSPCs). The resulting loss of antibody binding prompted the modification and humanization of the anti-CD45 antibody, culminating in the development of an anti-CD45 antibody-drug conjugate (CD45-ADC; CIM053-SG3376). In an AML mouse models xenografted with HSPCs, administration of the CD45-ADC selectively depleted human leukemia and HSPCs wt cells while preserving the healthy hematopoietic system derived from the transplanted base edited HSPCs.
Usage: In vitro antibody-drug-conjugate (ADC) mediated killing assays. For ADC killing assays involving saporin, a 100 nM stock was prepared by incubating the biotinylated antibody and Streptavidin-ZAP at a 1:1 molar ratio for 30 min at room temperature
Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD45.2-SAP (Cat. #IT-91)
Selective haematological cancer eradication with preserved haematopoiesis
Garaudé S, Marone R, Lepore R, Devaux A, Beerlage A, Seyres D, Dell’ Aglio A, Juskevicius D, Zuin J, Burgold T, Wang S, Katta V, Manquen G, Li Y, Larrue C, Camus A, Durzynska I, Wellinger LC, Kirby I, Van Berkel PH, Kunz C, Tamburini J, Bertoni F, Widmer CC, Tsai SQ, Simonetta F, Urlinger S, Jeker LT (2024) Selective haematological cancer eradication with preserved haematopoiesis. Nature 630(8017):728-735. doi: 10.1038/s41586-024-07456-3 PMID: 38778101
Objective: To demonstrate that an antibody–drug conjugate (ADC) targeting the pan-haematopoietic marker CD45 enables the antigen-specifc depletion of the entire haematopoietic system, including Haematopoietic stem cells ( HSC).
Summary: Pairing this ADC with the transplantation of human HSCs engineered to be shielded from the CD45-targeting ADC enables the selective eradication of leukaemic cells with preserved haematopoiesis. The combination of CD45-targeting ADCs and engineered HSCs creates an almost universal strategy to replace a diseased haematopoietic system, irrespective of disease aetiology or originating cell type.
Usage: For ADC killing assays involving saporin, a 100 nM stock was prepared by incubating the biotinylated antibody (BC8 or MIRG451 mAbs) and saporin–streptavidin (IT-27) at a 1:1 molar ratio for 30 min at room temperature
Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)
Streptavidin-drug conjugates streamline optimization of antibody-based conditioning for hematopoietic stem cell transplantation
Yelamali AR, Chendamarai E, Ritchey JK, Rettig MP, DiPersio JF, Persaud SP (2024) Streptavidin-drug conjugates streamline optimization of antibody-based conditioning for hematopoietic stem cell transplantation. bioRxiv 2024.02.12.579199. doi: 10.1101/2024.02.12.579199 PMID: 38405731
Objective: Use biotinylated CD45.2 antibodies conjugated to Streptavidin to target hematopoietic stem cells (HSCs) for HSC transplantation.
Summary: Hematopoietic stem cell transplantation offers a promising alternative to standard cancer treatments. Using Click Chemistry, different toxic payloads were attached to streptavidin and observed.
Usage: 75 micrograms of CD45.2 delivered to HSCs deriving from B6 mice.
Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)
Aging hematopoiesis: Functional insights and prospects for rejuvenation
Konturek-Ciesla A (2023) Aging hematopoiesis: Functional insights and prospects for rejuvenation. Lund University Thesis.
Objective: To examine the function of hematopoietic stem cells (HSCs), the source of all mature blood cells, during adulthood and upon aging.
Summary: A gradual decrease in HSCs multi-lineage differentiation capacity, with the most significant reduction in their lymphoid output. The decreased lymphopoiesis could be attributed to the lymphoid progenitor subset, MPP Ly-I, revealing defects in the HSCs transition to these cells. Hematopoietic rejuvenation techniques studied through HSCs and their aging processes.
Usage: Anti-CD45-SAP (IT-91) was delivered to ex vivo HSCs cells.
Related Products: Anti-CD45.2-SAP (Cat. #IT-91)
