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The bone marrow stroma in human myelodysplastic syndrome reveals alterations that regulate disease progression
Kfoury YS, Ji F, Jain E, Mazzola MC, Schiroli G, Papazian A, Mercier FE, Sykes DB, Kiem A, Randolph MA, Abdel-Wahab OI, Calvi LM, Sadreyev R, Scadden DT (2023) The bone marrow stroma in human myelodysplastic syndrome reveals alterations that regulate disease progression. Blood Adv bloodadvances.2022008268. doi: 10.1182/bloodadvances.2022008268 PMID: 37450380
Objective: Evaluate mesenchymal cell molecular features searching for modifications that could impact Myelodysplastic syndrome (MDS) and offer potential therapeutics.
Summary: MDS is a heterogenous group of diseases affecting hematopoietic stem cells and are curable only by stem cell transplantation. Animal models of MDS indicate that changes in specific mesenchymal progenitor subsets in the BM can induce or select for abnormal hematopoietic cells. The authors identified that osteopontin (SPP1) is overexpressed in human bone marrow mesenchymal cells. SPP1 expression in comparable mesenchymal stromal cell populations plays protective roles in disease progression in an MDS mouse model.
Usage: Streptavidin-ZAP was combined with biotinylated CD117 (cKit) Ab in a 1:1 molar ratio. Mice were dosed with the conjugate at 3 mg/kg. The authors used the antibody-drug conjugate as a conditioning strategy that spares the non-hematopoietic microenvironment in the BM from genotoxic injury. This approach has been shown to deplete host hematopoietic stem cells with minimal toxicity effectively.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age
Konturek-Ciesla A, Dhapola P, Zhang Q, Säwén P, Wan H, Karlsson G, Bryder D (2023) Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age. Cell Rep 42(4):112304. doi: 10.1016/j.celrep.2023.112304 PMID: 36961818
Objective: Using single-cell transcriptome and epitope profiling to study hematopoiesis and the effects from aging.
Summary: The contribution from Hematopoietic stem cells (HSCs) to mature blood cells decline with age. The authors used transcriptome and epitope profiling to reconstruct early hematopoiesis and assessed HSC-specific lineage tracing. Their analysis identified previously uncharacterized cell populations which included multipotent progenitor cells (MPP) Ly-1 and Ly-II. Flt3 is a marker indicative of early differentiation found on MPP cells and was targeted for elimination via an antibody to Flt3 combined with Streptavidin-ZAP. This cell depletion provided evidence for the lack of self-renewal of Ly-1 and Ly-II cells in a transplantation setting and suggests that they need to be continuously replenished by upstream HSPCs.
Usage: Biotinylated anti-CD135 (clone A2F10) was combined with Streptavidin-ZAP at a 1:1 molar ratio, diluted in PBS to 0.2 mg/ml and injected into mice at 3 mg/kg.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Streptavidin-saporin: Converting biotinylated materials into targeted toxins
Ancheta LR, Shramm PA, Bouajram R, Higgins D, Lappi DA (2023) Streptavidin-saporin: Converting biotinylated materials into targeted toxins. Toxins 15(3):181. doi: 10.3390/toxins15030181
Summary: This manuscript describes the myriad of ways Streptavidin-ZAP is used and how this technology supports the scientific process of ‘Molecular Surgery’ and progress in research and drug development. Insights from publications and research performed using Streptavidin-ZAP and its impact on academia and industry for research and drug development are presented.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
CD3e-immunotoxin spares CD62Llo Tregs and reshapes organ-specific T-cell composition by preferentially depleting CD3ehi T cells
Kim S, Shukla RK, Yu H, Baek A, Cressman SG, Golconda S, Lee GE, Choi H, Reneau JC, Wang Z, Huang CA, Liyanage NPM, Kim S (2022) CD3e-immunotoxin spares CD62Llo Tregs and reshapes organ-specific T-cell composition by preferentially depleting CD3ehi T cells. Front Immunol 13:1011190. doi: 10.3389/fimmu.2022.1011190
Objective: To use a new murine testing model to demonstrate a substantial enrichment of tissue-resident Foxp3+ Tregs following CD3e-IT treatment.
Summary: The multi-organ pharmacodynamics of CD3e-IT and potential treatment resistance mechanisms identified in this study may generate new opportunities to further improve this promising treatment.
Usage: Male C57BL/6J mice were injected into retro-orbital sinus with 15 μg S-CD3e-IT (Biotinylated Anti-CD3 mixed with Streptavidin-ZAP in sterile 200 μl PBS twice a day for four consecutive days.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
In vivo visualization and molecular targeting of the cardiac conduction system
Goodyer WR, Beyersdorf BM, Duan L, van den Berg NS, Mantri S, Galdos FX, Puluca N, Buikema JW, Lee S, Salmi D, Robinson ER, Rogalla S, Cogan DP, Khosla C, Rosenthal EL, Wu SM (2022) In vivo visualization and molecular targeting of the cardiac conduction system. J Clin Invest e156955. doi: 10.1172/jci156955
Objective: To engineer targeted antibody conjugates directed against the cardiac conduction system (CCS) to allow visualization of the CCS in vivo.
Summary: Accidental injury to the CCS, a specialized set of cells embedded within the heart and indistinguishable from the surrounding heart muscle tissue, is a major complication in cardiac surgeries. They generated a fully human monoclonal Fab (hCNTN2) that targets the CCS with high specificity.
Usage: Streptavidin-ZAP was reacted with biotinylated hCNTN2 Fab to create hCNTN2-SAP. 100 ug of either hCNTN2-SAP and control-SAP were injected into wild-type mice with a single tail-vein injection and hearts were harvested after 2 days.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Antibody-based preparative regimens for cell, tissue and organ transplantation
Van Hentenryck M, Li Z, Murphy PM, Czechowicz A (2022) Antibody-based preparative regimens for cell, tissue and organ transplantation. (eds. 162). OBM Transplantation 6(3):162. doi: 10.21926/obm.transplant.2203162
Objective: Provide a review of progress in the use of antibodies to support cell and tissue transplantation with a particular focus on induction of donor-specific tolerance for solid organ transplantation.
Summary: Antibody-based conditioning to prepare the recipient is a promising approach towards achieving transplant tolerance in both hematopoietic and solid organ transplant settings.
Usage: To enhance HSC depletion while avoiding bystander toxicity (neutropenia, lymphopenia, and thrombocytopenia) caused by CD45-radioimmunotherapy, Palchaudhuri et al. developed a saporin-based CD45 (CD45-SAP) immunotoxin using a biotinylated antibody and Streptavidin-ZAP.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
See Also:
- Palchaudhuri R Featured Article: Targeted depletion of hematopoietic stem cells promises safer transplantation. Targeting Trends 17(3), 2016.
- 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.
Comparison of CD3e antibody and CD3e-sZAP immunotoxin treatment in mice identifies szap as the main driver of vascular leakage
Kim S, Shukla RK, Kim E, Cressman SG, Yu H, Baek A, Choi H, Kim A, Sharma A, Wang Z, Huang CA, Reneau JC, Boyaka PN, Liyanage NPM, Kim S (2022) Comparison of CD3e antibody and CD3e-sZAP immunotoxin treatment in mice identifies szap as the main driver of vascular leakage. Biomedicines 10(6):1221. doi: 10.3390/biomedicines10061221
Objective: Investigate and identify the toxicity profiles of a CD3e-mAb and an immunotoxin of this CD3e antibody conjugated to saporin via a biotin-streptavidin bond, S-CD3e-IT.
Summary: The two agents had opposite effects on T cells, with the antibody alone able to modulate CD3e on the cell surface while the S-CD3e-IT caused depletion of the cell. The immunotoxin increased the infiltration of polymorphonuclear leukocytes (PMNs) into the tissue parenchyma of the spleen and lungs, a sign of vascular permeability while the antibody alone showed no signs of vascular leakage.
Usage: S-CD3e-IT was prepared by reacting biotinylated CD3e antibody with Streptavidin-ZAP in a 1:1 molar ratio. C57BL/6J mice received 25 μg of S-CD3e-IT in sterile 200 μL PBS, twice a day via retro-orbital injection for four days.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Antibody-drug conjugates plus Janus kinase inhibitors enable MHC-mismatched allogeneic hematopoietic stem cell transplantation
Persaud SP, Ritchey JK, Kim S, Lim S, Ruminski PG, Cooper ML, Rettig MP, Choi J, DiPersio JF (2021) Antibody-drug conjugates plus Janus kinase inhibitors enable MHC-mismatched allogeneic hematopoietic stem cell transplantation. J Clin Invest 131(24):e145501. doi: 10.1172/JCI145501
Objective: To demonstrate that biotinylated anti-CD45-SAP or anti-cKit-SAP mixed with Streptavidin-Saporin along with Janus kinase 1/2, enables alloengraftment on murine allo-hematopoietic stem cell transplantation (HSCT) models.
Summary: HSCT has therapeutic potential. However, the transplantation requires first depletion and secondly, for allogeneic-HCST, host and immune responses need to be controlled to prevent graft rejection. The allo-HSCT conditioning strategy exemplifies the promise of immunotherapy to improve the safety of HSCT for treating hematologic diseases.
Usage: Antibodies were incubated with Streptavidin-ZAP (1:1 molar ratio) for 15 minutes at 20°C and . The doses of CD45.2 and cKit conjugates were injected retroorbitally (41.8 μg and 33.2 μg, respectively).
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Enhancing the therapeutic potential of extracellular vesicles using peptide technology
Martin Perez C, Conceição M, Raz R, Wood MJA, Roberts TC (2022) Enhancing the therapeutic potential of extracellular vesicles using peptide technology. (eds. Langel Ü). In: Cell Penetrating Peptides. Methods in Molecular Biology 2383:119-141. Humana, New York, NY. doi: 10.1007/978-1-0716-1752-6_8
Objective: To modify EVs with peptides which confer specific advantageous properties, thus enhancing their therapeutic potential.
Summary: The authors provide an overview of the applications of peptide technology with respect to EV therapeutics. We focus on the utility of EV-modifying peptides for the purposes of promoting cargo loading, tissue-targeting and endosomal escape, leading to enhanced delivery of the EV cargo to desired cells/tissues and subcellular target locations. Both endogenous and exogenous methods for modifying EVs with peptides are considered.
Usage: Streptavidin-ZAP is combined with biotinylated peptides to make a targeted saporin conjugate.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Light-controlled elimination of PD-L1+ cells
Wong JJW, Selbo PK (2021) Light-controlled elimination of PD-L1+ cells. J Photochem Photobiol B 225:112355. doi: 10.1016/j.jphotobiol.2021.112355
Objective: To investigate novel strategies that simultaneously target both tumor cells and immunosuppressive cells in the tumor microenvironment. The focus was on the evaluation in vitro of Anti-PD-L1-SAP combined with photochemical internalization (PCI) as a therapeutic strategy to target and eliminate PD-L1 expressing tumor and immunosuppressive cells.
Summary: The authors show that the intracellular light-controlled drug delivery method induces specific and strongly enhanced cytotoxic effects of Anti-PD-L1-SAP in the PD-L1+ triple-negative breast cancer MDA-MB-231 cell line, while no enhanced efficacy was obtained in the PD-L1 negative control cell line MDA-MB-453.
Usage: Anti-PD-L1-SAP and Streptavidin-ZAP (Control) were used in a cytotoxicity assay.
Related Products: Anti-PD-L1-SAP (Cat. #IT-45), Streptavidin-ZAP (Cat. #IT-27)