zap-conjugates

Hickerson BT, Daniels-Wells TR, Payes C, Clark LE, Candelaria PV, Bailey KW, Sefing EJ, Zink S, Ziegenbein J, Abraham J, Helguera G, Penichet ML, Gowen BB (2022) Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections. Nat Commun 13(1):558. doi: 10.1038/s41467-021-27949-3 PMID: 35091550

Objective: Demonstrate that a fusion protein of the antibody (ch128.1/IgG1) directed against the apical domain of human transferrin receptor 1 (hTfR1) and the Machupo virus (MACV) can inhibit infection of attenuated and pathogenic New World mammarenaviruses (NWMs).

Summary: NWMs cause life-threatening hemorrhagic fever (HF) and these viruses enter into cells via hTfR1. Use of ch128.1/IgG1 with other promising direct-acting small molecule antivirals or antibodies targeting the viral envelope glycoprotein would provide a complementary therapeutic strategy that would increase efficacy and reduce the emergence of drug resistance.

Usage: References MonoBiotin-ZAP reacted with avidinylated anti-hTfR (ch128.1Av) in a 1:1 molar ratio on ice for 30 minutes.

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP)

See Also:

• Daniels-Wells TR et al. Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1. Toxicol In Vitro 27(1):220-231, 2013.
• Daniels TR et al. Conjugation of an anti transferrin receptor IgG3-avidin fusion protein with biotinylated saporin results in significant enhancement of its cytotoxicity against malignant hematopoietic cells. Mol Cancer Ther 6:2995-3008, 2007.

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)

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)

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)

Lodhi MS, Khan MT, Bukhari SMH, Sabir SH, Samra ZQ, Butt H, Akram MS (2021) Probing transferrin receptor overexpression in gastric cancer mice models. ACS Omega 6(44):29893-29904. doi: 10.1021/acsomega.1c04382 PMID: 34778662

Objective: To investigate the role of the transferrin receptor, a glycoprotein receptor that is expressed many-folds on rapidly growing cells due to the greater demand of iron, in gastric cancer.

Summary: A mouse model of gastric cancer has the potential to be used in the future to study the therapeutic effects of cancer medicines, and overexpression of transferrin receptors could be identified through the designed probe to be used as diagnostics.

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP)

See Also:

• Daniels TR et al. Conjugation of an anti transferrin receptor IgG3-avidin fusion protein with biotinylated saporin results in significant enhancement of its cytotoxicity against malignant hematopoietic cells. Mol Cancer Ther 6:2995-3008, 2007.

Bloch JS, Sequeira JM, Ramírez AS, Quadros EV, Locher KP (2021) Generation of nanobodies targeting the human, transcobalamin-mediated vitamin B12 uptake route. bioRxiv 2021.08.16.456495. doi: 10.1101/2021.08.16.456495

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

Iida K, Abdelhamid Ahmed AH, Nagatsuma AK, Shibutani T, Yasuda S, Kitamura M, Hattori C, Abe M, Hasegawa J, Iguchi T, Karibe T, Nakada T, Inaki K, Kamei R, Abe Y, Nomura T, Andersen JL, Santagata S, Hemming ML, George S, Doi T, Ochiai A, Demetri GD, Agatsuma T (2021) Identification and therapeutic targeting of GPR20, selectively expressed in gastrointestinal stromal tumorswith DS-6157a, a first-in-class antibody-drug conjugate. Cancer Discov 11(6):1508-1523. doi: 10.1158/2159-8290.Cd-20-1434 PMID: 33579785

Objective: Introduce DS-6157a, an anti-GPR20 antibody-drug therapeutic for gastrointestinal stromal tumors (GIST).

Summary: The only approved treatments for GIST are currently tyrosine kinase inhibitors (TKI) which can be problematic. They lead to secondary resistance mutations in KIT or PDGFRA and disease progression. The authors identified G protein-coupled receptor 20 (GPR20) as a non-tyrosine kinase target and assessed its expression in cell lines, xenografts, and clinical samples. Preclinical pharmacokinetics and safety profile support its development as a novel GIST therapy.

Usage: Internalization activity of anti-GPR20 mAbs were evaluated by using Rat-ZAP. GPR20-expressing 293T cells were plated at 2500 cells/well in 96-well plates. Cells were treated with dilutions of various anti-GPR20 and 500 ng/ml of Rat-ZAP for 3 days. The percentage of living cells were measured using a CellTiter-Glo Luminescent Cell Viability Assay.

Related Products: Rat-ZAP (Cat. #IT-26)

Penna S, Villa A, Capo V (2021) Autosomal recessive osteopetrosis: mechanisms and treatments. Dis Model Mech 14(5):dmm048940. doi: 10.1242/dmm.048940

Summary: Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease characterized by defective osteoclast resorption or differentiation. Novel therapeutic approaches are needed for ARO patients. The authors review preclinical and proof-of-concept studies, such as gene therapy, systematic administration of deficient protein, in utero Hematopoietic stem cell transplantation (HSCT) and gene editing.

Usage: Efficacy in HSCT conditioning was demonstrated with CD45.2-SAP (biotinylated Anti-CD45 mixed with Streptavidin-ZAP). In mice, CD45.2–SAP preserved normal bone marrow architecture compared to total body irradiation, which instead reduced vascular integrity and bone marrow cellularity. Mice conditioned with CD45.2–SAP rapidly recovered their peripheral myeloid cells and had a survival advantage when exposed to infections (3 mg/kg iv; Palchaudhuri et al.). Additionally, conditioning with CD45.2–SAP resulted in significant chimerism after transplantation, even in a pathological mouse model (3 mg/kg iv; Castiello et al.).

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

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.

Wang D, Shao X, Wang Q, Pan X, Dai Y, Yao S, Yin T, Wang Z, Zhu J, Xi X, Chen Z, Chen S, Zhang G (2021) Activated factor X targeted stored in platelets as an effective gene therapy strategy for both hemophilia A and B. Clin Transl Med 11(3):e375. doi: 10.1002/ctm2.375

Summary: Treatment of hemophiliacs with inhibitors remains challenging, and new treatments are in urgent need. Coagulation factor X plays a critical role in downstream blood coagulation cascade, which could serve as a bypassing agent for hemophilia therapy. Target expression of the FXa precursor to platelets can generate a storage pool of FXa in platelet α-granules, the platelet-stored FXa is effective in treating HA and HB with inhibitors, suggesting that this could be a novel choice for hemophilia patients with inhibitors.

Usage: A single dose of CD45.2-SAP (biotinylated Anti-CD45 mixed with Streptavidin-ZAP) enabled efficient engraftment of donor cells (> 90%) and full correction of sickle-cell anemia. (3 mg/kg iv; Palchaudhuri et al.).

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.

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

Koeniger T, Bell L, Mifka A, Enders M, Hautmann V, Mekala SR, Kirchner P, Ekici AB, Schulz C, Wörsdörfer P, Mencl S, Kleinschnitz C, Ergün S, Kuerten S (2021) Bone marrow-derived myeloid progenitors in the leptomeninges of adult mice. Stem Cells 39(2):227-239. doi: 10.1002/stem.3311

Summary: This report confirms the presence of myeloid progenitors at the meningeal border of the brain and lays the foundation to unravel their possible functions in CNS surveillance and local immune cell production. Compared to bone marrow transfer after whole-body irradiation, chimerism developed more slowly in the CD45-SAP (biotinylated anti-CD45 mixed with Streptavidin-ZAP) model and only reached around 50% in the blood myeloid compartment 15 weeks after 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.

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