Zhao Q, Zong H, Zhu P, Su C, Tang W, Chen Z, Jin S (2024) Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs. Exp Hematol Oncol 13(1):6. doi: 10.1186/s40164-024-00474-x PMID: 38254219

Summary: Cancer immunotherapy has become a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy. Cancer stem cells (CSCs) have the capabilities of self-renewal and differentiation and are also resistant to the traditional therapies of radiotherapy and chemotherapy. The authors review strategies for targeting colorectal CSCs, where one method described uses a biotinylated antibody against EpCAM (clone 3-171) conjugated to saporin via Streptavidin-ZAP (IT-27).

Related Products: Streptavidin-ZAP (Cat. #IT-27)

See Also:

• Lund K et al. The novel EpCAM-targeting monoclonal antibody 3-17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines. MAbs 6(4):1038-1050, 2014.

Canarutto D, Omer Javed A, Pedrazzani G, Ferrari S, Naldini L (2023) Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation. Br Med Bull ldad017. doi: 10.1093/bmb/ldad017 PMID: 37460391

Objective: The authors review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.

Summary: In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient’s. Ex vivo HSC gene therapy (HSC GT) is a form of HSCT in which HSCs are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow niche, which is required for the engraftment of infused cells. One approach reviewed by the authors involves Anti-CD45-SAP. The conjugate was shown to clear the white blood cell compartment. Administration into mice prior to HSCT resulted in comparable haematopoietic reconstitution as total body irradiation, with less side effects (Palchaudhuri R. et al, 2016) and faster T-cell repopulation likely due to sparing radio damage to the thymic stroma (Schiroli G et al., 2017).

Related Products: 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.
• Schiroli G et al. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Sci Transl Med 9(411):eaan0820, 2017.

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)

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)

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.

Griffin JM, Healy FM, Dahal LN, Floisand Y, Woolley JF (2022) Worked to the bone: antibody-based conditioning as the future of transplant biology. J Hematol Oncol 15(1):65. doi: 10.1186/s13045-022-01284-6

Objective: To analyze the current status of antibody-based drugs in pre-transplant conditioning regimens and assess their potential in the future of transplant biology.

Summary: This review article suggests that antibody-based conditioning regimens may be the next big advancement in hematopoietic stem cell transplantation.

Related Products: Anti-CD117-SAP (Cat. #IT-83)

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.
• Castiello MC et al. Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. J Allergy Clin Immunol 147(1):309-320.e6, 2021.
• 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.
• Li Z et al. Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation. Nat Commun 10:616, 2019.

Charlesworth CT, Hsu I, Wilkinson AC, Nakauchi H (2022) Immunological barriers to haematopoietic stem cell gene therapy. Nat Rev Immunol 1-15. doi: 10.1038/s41577-022-00698-0

Objective: This review article attempts to encourage more research to address the immunological barriers to haematopoietic stem cell based gene therapies.

Summary: The authors lay out the history and clinical trials of hematopoietic stem cell gene therapy and then discuss the challenges of both innate immunity and adaptive immunity.

Usage: This review mentions a publication that used Anti-CD117-SAP to ablate hematopoietic stem cells.

Related Products: Anti-CD117-SAP (Cat. #IT-83)

See Also:

• 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.

Saha A, Hyzy S, Lamothe T, Hammond K, Clark N, Lanieri L, Bhattarai P, Palchaudhuri R, Gillard GO, Proctor J, Riddle MJ, Panoskaltsis-Mortari A, MacMillan ML, Wagner JE, Kiem HP, Olson LM, Blazar BR (2022) A CD45-targeted antibody-drug conjugate successfully conditions for allogeneic hematopoietic stem cell transplantation in mice. Blood 139(11):1743-1759. doi: 10.1182/blood.2021012366 PMID: 34986233

Objective: To investigate the effectiveness of a CD45-targeted antibody-drug conjugate (ADC) in conditioning for allogeneic hematopoietic stem cell transplantation (HSCT) in mice.

Summary: In this study, researchers evaluated a novel CD45-targeted antibody-drug conjugate as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in mice. The results demonstrated successful conditioning, highlighting the potential of this approach for improving the outcomes of allogeneic HSCT in the future.

Related Products: Anti-CD117-SAP (Cat. #IT-83)

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.
• Li Z et al. Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation. Nat Commun 10:616, 2019.
• Gao C et al. Nongenotoxic antibody-drug conjugate conditioning enables safe and effective platelet gene therapy of hemophilia A mice. Blood Adv 3(18):2700-2711, 2019.
• Castiello MC et al. Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. J Allergy Clin Immunol 147(1):309-320.e6, 2021.

Napoli M, Wu SJ, Gore BL, Abbas HA, Lee K, Checker R, Dhar S, Rajapakshe K, Tan AC, Lee MG, Coarfa C, Flores ER (2022) ΔNp63 regulates a common landscape of enhancer associated genes in non-small cell lung cancer. Nat Commun 13(1):614. doi: 10.1038/s41467-022-28202-1 PMID: 35105868

Objective: To investigate the underlying mechanistic role regulated by ΔNp63 in lung cancer development.

Summary: Use of a ΔNp63-specific conditional knockout mouse model and xenograft models of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results show that ΔNp63 promotes non-small cell lung cancer by maintaining the lung stem cells necessary for lung cancer cell initiation and progression in quiescence. ΔNp63 regulates enhancers of cell identity genes.

Usage: Immunofluorescence and IHC (1:100)

Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

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)