Ren X, Wang Y, Zhang Y (2025) Targeted depletion of dysfunctional hematopoietic stem cells mitigates myeloid-biased differentiation in aged mice. Cell Discov 11:56. doi: 10.1038/s41421-025-00810-3 PMID: 40490480
Objective: To develop and evaluate a targeted strategy for depleting dysfunctional, myeloid-biased CD150-high hematopoietic stem cells (HSCs) in aged mice to restore balanced hematopoiesis and mitigate aging-related blood disorders.
Summary: The study used an antibody-toxin conjugate to selectively eliminate CD150-high HSCs, improving lymphoid-to-myeloid ratios, reducing platelet hyperproduction, and restoring hematopoietic balance in aged mice. Treatment preserved functional CD150-low HSCs and showed minimal off-target or systemic toxicity.
Usage: Streptavidin-ZAP (IT-27) was combined with a biotinylated anti-CD150 antibody to generate Anti-CD150-SAP (IT-103). This conjugate was used at doses of 1–2 mg/kg in vivo and as low as 0.01 nM in vitro to specifically deplete CD150-high HSCs while sparing CD150-low populations.
Movahed AY, Bagheri R, Savatier P, Šarić T, Moradi S (2025) Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy. Stem Cell Reports 102543. doi: 10.1016/j.stemcr.2025.102543 PMID: 40541178
Objective: To review and evaluate current strategies for eliminating tumorigenic pluripotent stem cells (PSCs) from differentiated cell therapy products to improve the safety of PSC-based regenerative therapies.
Summary: Residual undifferentiated PSCs pose a tumorigenic risk in cell therapies. This review outlines genetic, antibody, toxin, and small molecule strategies for selectively removing PSCs, emphasizing the need for efficient, selective methods to ensure safety in regenerative medicine.
Usage: References a previous study that used Fab-ZAP to eliminate pluripotent stem cells by targeting specific surface markers, demonstrating its application as a targeted immunotoxin for PSC depletion.
Dib C, Queenan J, Willner H, Swartzrock L, Charlesworth C, Denis M, Davis J, Nakauchi H, Liu DR (2025) Combining hsc base-editing with anti-cd117 antibody conditioning to correct severe combined immunodeficiency disorder in a novel mouse model. Transplantation and Cellular Therapy 31(2):S253-S354. doi: 10.1016/j.jtct.2025.01.385
Objective: To test whether base-edited hematopoietic stem cells (HSPCs) combined with non-genotoxic antibody conditioning can correct severe combined immunodeficiency (SCID) in a novel Rag2 mutant mouse model.
Summary: Base-editing delivered via engineered virus-like particles successfully corrected Rag2 mutations in HSPCs, which restored lymphocyte development following transplantation. Conditioning with an Anti-CD117-Saporin conjugate enabled efficient engraftment without irradiation toxicity, demonstrating a safer strategy for SCID treatment.
Usage: Mice were conditioned with Anti-CD117-SAP (IT-83) at 1.5 mg/kg intravenously prior to transplantation of base-edited or wild-type HSPCs.
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.
Limonta P, Chiaramonte R, Casati L (2024) Unveiling the dynamic interplay between cancer stem cells and the tumor microenvironment in melanoma: Implications for novel therapeutic strategies. Cancers (Basel) 16(16):2861. doi: 10.3390/cancers16162861 PMID: 39199632
Objective: To review the bidirectional communication between melanoma cancer stem cells (CSCs) and the tumor microenvironment, highlighting its role in drug resistance and tumor relapse.
Summary: Melanoma CSCs evade immune surveillance and recruit immune cells with immunosuppressive and tumor-promoting properties, establishing a supportive microenvironment. They also transfer stemness and aggressive traits to neighboring non-CSCs, driving tumor progression and metastasis. Targeting these interactions may offer novel therapeutic strategies for combating melanoma.
Usage: This review publication highlights the usage of Anti-CD271-SAP and CD133-SAP in previous publications.
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).
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
Pandala N, Han I, Meyering E, Stone EM, Mullins RF, Tucker BA (2024) iPSC derived choroidal endothelial cell delivery using laminin-based hydrogels for the treatment of AMD. ARVO Annual Meeting 65(7):1542.
Objective: To demonstrate an interventional therapy for age-related macular degeneration (AMD) using a rat model.
Summary: In this study, induced pluripotent stem cells (iPSCs) were injected into the eyes of rats that had undergone Anti-CD105-SAP-induced choroidal cell death, mimicking the pathology of AMD. The efficacy of the iPSC treatment was evaluated by comparing donor cell survival, retention, and integration in treated eyes versus controls that did not receive iPSCs.
Usage: Anti-CD105-SAP (IT-80) was administered via supra-choroidal injection at a concentration of 0.05 mg/ml to selectively induce choroidal endothelial cell death.
Kitawi R, Ledger S, Kelleher AD, Ahlenstiel CL (2024) Advances in HIV gene therapy. Int J Mol Sci 25(5):2771. doi: doi.org/10.3390/ijms25052771
Objective: This review highlights the various stages of ex vivo gene therapy, current research developments that have increased the efficiency and safety of this process, and a comprehensive summary of Human Immunodeficiency Virus (HIV) gene therapy studies, the majority of which have employed the ex vivo approach.
Summary: The long-term or permanent expression of anti-HIV genes and the modification of CD4+ and CD34+ cells to render them resistant to infection or to allow the disruption of the HIV life cycle are important strategies in the quest to achieve a HIV cure.
Usage: Authors referenced CD117 antibody conjugated to saporin via streptavidin (IT-27, IT-83), which enabled >99% depletion of endogenous HSCs in NSG mice and non-human primates.
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.
