Chan YY, Ho PY, Swartzrock L, Rayburn M, Nofal R, Thongthip S, Weinberg KI, Czechowicz A (2023) Non-genotoxic restoration of the hematolymphoid system in fanconi anemia. Transplant Cell Ther 29(3):164.e1-164.e9. doi: 10.1016/j.jtct.2022.08.015 PMID: 35995393

Objective: Evaluate the efficacy of different CD117 mAb agents and immunosuppression on hematopoietic stem cell (HSC) depletion, and their ability to safely establish therapeutic donor hematopoiesis post-HSCT in Fancomi Anemia (FA) disease models.

Summary: Patients with FA are particularly sensitive to genotoxic agents in the treatment of blood and immune diseases. By targeting the disease through use of a CD117 antibody conjugate to an antagonist agent, some of the sensitivities of Fancomi anemia can be circumvented compared to traditional therapeutics. The results demonstrated the efficacy of several different non-genotoxic monoclonal antibody-based conditioning strategies in Fancomi anemia.

Usage: Biotinylated CD117 mAb mixed with Streptavidin-ZAP (Anti-CD117-SAP) and was administered on Day 0. Anti-CD117-SAP was diluted with sterile PBS and administered at 1.5 mg/kg via i.v. injection.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)

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.

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.

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.

Skulimowska I, Sosniak J, Gonka M, Szade A, Jozkowicz A, Szade K (2021) The biology of hematopoietic stem cells and its clinical implications. FEBS J 16192. doi: 10.1111/febs.16192

Objective: To review the opportunities and challenges of recent findings to improve the clinical use of hematopoietic stem cells (HSCs)

Summary: The authors describe new methods of HSC mobilization and conditioning for transplantation and highlight research that may lead to solutions for the limitations of HSC transplantation

See: 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.

Read the featured article in Targeting Trends.

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

Srikanthan MA, Humbert O, Haworth KG, Ironside C, Rajawat YS, Blazar BR, Palchaudhuri R, Boitano AE, Cooke MP, Scadden DT, Kiem HP (2020) Effective multi-lineage engraftment in a mouse model of fanconi anemia using non-genotoxic antibody-based conditioning. Mol Ther Methods Clin Dev 17:455-464. doi: 10.1016/j.omtm.2020.02.001 PMID: 32226796

Objective: To utilize antibody-drug conjugates (ADC) as an alternative conditioning regimen in a Fanconi anemia (FA) mouse model of autologous transplantation.

Summary: Antibody conjugates targeting hematopoietic cells are an emerging non-genotoxic method of promoting engraftment of transplanted cells while maintaining intact marrow cellularity. FANCA knockout mice were conditioned with either Anti-CD45-SAP or Anti-CD117-SAP prior to receiving whole marrow from a heterozygous healthy donor. Bone marrow and peripheral blood analysis revealed equivalent levels of donor engraftment, with minimal toxicity in ADC-treated groups as compared with cyclophosphamide-treated control.

Usage: Anti-CD45-SAP (3 mg/kg total complex) or Anti-CD117-SAP (1.5 mg/kg total complex) via tail vein injection.

Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Anti-CD117-SAP (Cat. #IT-83)

Czechowicz A, Palchaudhuri R, Scheck A, Hu Y, Hoggatt J, Saez B, Pang WW, Mansour MK, Tate TA, Chan YY, Walck E, Wernig G, Shizuru JA, Winau F, Scadden DT, Rossi DJ (2019) Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617. doi: 10.1038/s41467-018-08201-x

Objective: To investigate a safe and effective method for hematopoietic stem cell transplantation.

Summary: CD117-ADC selectively targets hematopoietic stem cells yet does not cause clinically significant side-effects.

Usage: The CD117-ADC was prepared by combining biotinylated anti-CD117 (clone 2B8) with Streptavidin–ZAP. A dose of 1.5 mg/kg of CD117-ADC (~12 µg Streptavidin-ZAP) optimally resulted in depletion of >99% of immunophenotypic and functional HSCs.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)