zap-conjugates

Persaud SP, Ritchey JK, Choi J, Ruminski PG, Cooper ML, Rettig MP, DiPersio JF (2020) Antibody-drug conjugates targeting CD45 plus Janus kinase inhibitors effectively condition for allogeneic hematopoietic stem cell transplantation. bioRxiv 2020.10.02.324475. doi: 10.1101/2020.10.02.324475

Related Products: Streptavidin-ZAP (Cat. #IT-27), Blank-Streptavidin-SAP (Cat. #IT-27B)

Su Y, Zhang X, Bidlingmaier S, Behrens CR, Lee NK, Liu B (2020) ALPPL2 is a highly specific and targetable tumor cell surface antigen. Cancer Res 80(20):4552-4564. doi: 10.1158/0008-5472.CAN-20-1418 PMID: 32868383

Objective: To evaluate therapeutic potential of ALPPL2 targeting.

Summary: Exquisite tissue specificity and broad tumor type coverage suggest that ALPPL2 could be an excellent cell surface target for therapeutic development against mesothelioma.

Usage: Biotinylated M25 IgG1 and Streptavidin-ZAP were mixed at a molar ratio of 1:1.

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

Gao C, Schroeder JA, Xue F, Jing W, Cai Y, Scheck A, Subramaniam S, Rao S, Weiler H, Czechowicz A, Shi Q (2019) Nongenotoxic antibody-drug conjugate conditioning enables safe and effective platelet gene therapy of hemophilia A mice. Blood Adv 3(18):2700-2711. doi: 10.1182/bloodadvances.2019000516

Objective: To determine whether hematopoietic cell–targeted ADC preconditioning is effective for engraftments that are genetically manipulated by 2bF8 lentivirus (2bF8LV) and whether sustained therapeutic platelet FVIII expression is attainable in platelet-specific gene therapy utilizing ADC-based preconditioning.

Summary: The authors describe targeted nongenotoxic preconditioning for 2bF8 gene therapy utilizing  a hematopoietic cell–specific antibody-drug conjugate (ADC), which consists of saporin conjugated to CD45.2- and CD117-targeting antibodies.

Usage: ADCs were prepared by combining biotinylated antibody with Streptavidin-ZAP.  The combination of CD45.2-ADC (3 mg/kg) plus CD117-ADC (0.5 mg/kg), with or without additional CD4-ADC (0.5 mg/kg) or CD8-ADC (0.5 mg/kg), was administered IV to 5- to 6-week-old FVIIInull/CD45.2 recipients 2 days before transplantation.

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

Lelieveldt L (2019) Chemical strategies for antigen-selective targeting of autoreactive B Cells. Chapter 2: Sequential prodrug strategy to target and eliminate ACPA-selective autoreactive B cells. Radboud Universiteit Nijmegen Nijmegen, Netherlands 45-64. Thesis.

Objective: To develop a method to target and selectively eliminate autoreactive B cells that produce anti-citrullinated proteins antibodies (ACPA) using a sequential antigen prodrug targeting strategy, as a treatment for Rheumatoid Arthritis (RA).

Summary: The study used a synthesized cyclic citrullinated peptide (CCP) antigen suitable for BCR binding and demonstrated that binding by ACPA was impaired upon introduction of a carboxy-pnitrobenzyl (CNBz) caging group at the side chain of the citrulline residue. Enzymatic reduction of the CNBz moiety by nitroreductase fully restored citrulline-selective recognition by both ACPA and ACPA-expressing B cells and showed targeted cell death of CCP-recognizing B cells only. These results mark an important step towards antigen-selective B cell targeting in general and more specifically in RA.

Usage: Streptavidin-ZAP mixed with biotinylated CCP peptides was tested in cytotoxicity assays. The exposure of cells to CCP-SA-ZAP at 1 nM as well as the activated CCP(CNBz) induced death of up to 60% of ACPA-expressing B cells.

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

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)

Li Z, Czechowicz A, Scheck A, Rossi DJ, Murphy PM (2019) Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation. Nat Commun 10:616. doi: 10.1038/s41467-018-08202-w

Objective: To develop a conditioning protocol for fully MHC-mismatched bone marrow allotransplantation in mice involving transient immunosuppression and selective depletion of recipient hematopoietic stem cells.

Summary: CD117-ADC conditioning promotes skin allograft tolerance.

Usage: Biotinylated monoclonal antibodies directed against mouse CD117 were coupled to Streptavidin-ZAP. Each mouse was injected with 1.5 mg/kg of ADC in a total volume of 300 mcl PBS.

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

Plum T (2019) Identification of lineage-specific markers for therapeutic targeting of mast cells. Ruperto-Carola University of Heidelberg, Germany Thesis. doi: 10.11588/heidok.00023555

Usage: Mice were injected i.v. with either 100 µg of 1:1 molar mixture of biotinylated CD63 antibody and Streptavidin-ZAP (60 µg mAb + 40 µg SAP) or with 40 µg SAP alone. All injections were performed in 200 µl PBS.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)

Säwen P, Eldeeb M, Erlandsson E, Kristiansen TA, Laterza C, Kokaia Z, Karlsson G, Yuan J, Soneji S, Mandal PK, Rossi DJ, Bryder D (2018) Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging. Elife 7:e41258. doi: 10.7554/elife.41258 PMID: 30561324

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

Berhani O, Glasner A, Kahlon S, Duev-Cohen A, Yamin R, Horwitz E, Enk J, Moshel O, Varvak A, Porgador A, Jonjic S, Mandelboim O. (2019) Human anti-NKp46 antibody for studies of NKp46-dependent NK cell function and its applications for type 1 diabetes and cancer research. Eur J Immunol 49(2):228-241. doi: 10.1002/eji.201847611 PMID: 30536875

Objective: To investigate human NKp46 activity and its critical role in Natural Killer (NK) cell biology.

Summary: A unique anti-human NKp46 monoclocal antibody was developed and conjugated to Saporin. Targeted toxin inhibits growth of NKp46-positive cells; thus, exemplifying the potential as an immunotherapeutic drug to treat NKp46-dependent diseases, such as, type I diabetes and NK and T cell related malignancies.

Usage: Conjugation of the antibodies to Saporin, treatment of cells, and cell viability assay Biotin-Z Kit instructions.

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

Lelieveldt LPWM, Kristyanto H, Pruijn GJM, Scherer HU, Toes REM, Bonger KM (2018) Sequential prodrug strategy to target and eliminate ACPA-selective autoreactive B cells. Mol Pharm 15(12):5565-5573. doi: 10.1021/acs.molpharmaceut.8b00741

Objective: To develop a method to target and selectively eliminate autoreactive B cells using a sequential antigen prodrug targeting strategy.

Summary: The selectivity of the antigen and the possibility to block binding toward circulation ACPA brings us a step closer to the specific elimination of autoreactive B cells for the treatment of patients with ACPA-positive RA.

Usage: Biotinylated CCP1, CArgP1, and CCP1(CNBz) were conjugated with Streptavidin-ZAP in a 4:1 ratio to make peptide-drug conjugates.

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