zap-conjugates

Marquez J, Dong J, Dong C, Tian C, Serrero G (2021) Identification of prostaglandin F2 receptor negative regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development. PLoS One 16(1):e0246197. doi: 10.1371/journal.pone.0246197

Summary: PTGFRN is a cell-surface protein that is upregulated in certain cancer types, including head and neck and, notably, pediatric medulloblastoma, an aggressive cancer with limited therapeutic options. With the selection of the mouse monoclonal antibody 33B7, the authors identified PTGFRN as a potential therapy target, and show that it is internalized by incubation with 33B7. Purified 33B7 antibody was sent to Advanced Targeting Systems where saporin was directly conjugated to the Fc region of 33B7 using their proprietary cleavable linker.

Usage: In a 96-well plate, 2000 cells/well were plated in triplicate in 100 μL of DMEM/F12 medium supplemented with 2.5% FBS, 0.4 ug/ml 33B7 antibody, and 0.9ug/ml of Fab-ZAP mouse. As an isotype control, cells were incubated with mouse Fab IgG-SAP as control (instead of 33B7) and Fab-ZAP.

Related Products: Fab-ZAP mouse (Cat. #IT-48), Fab IgG-SAP (Cat. #IT-67), Custom Conjugates

Castiello MC, Bosticardo M, Sacchetti N, Calzoni E, Fontana E, Yamazaki Y, Draghici E, Corsino C, Bortolomai I, Sereni L, Yu HH, Uva P, Palchaudhuri R, Scadden DT, Villa A, Notarangelo LD (2021) Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. J Allergy Clin Immunol 147(1):309-320.e6. doi: 10.1016/j.jaci.2020.04.033

Objective: To improve multi-lineage engraftment using non-genotoxic conditioning with Anti-CD45-Saporin.

Summary: Conditioning with Anti-CD45 antibody-drug conjugates may represent a novel and safe conditioning regimen for patients with RAG deficiency and other inborn errors of immunity.

Usage: Intravenous injection of Anti-CD45-SAP (3 mg/kg).

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

Fischer A, Wolf I, Fuchs H, Masilamani AP, Wolf P (2020) Pseudomonas Exotoxin A based toxins targeting epidermal growth factor receptor for the treatment of prostate cancer. Toxins (Basel) 12(12):753. doi: 10.3390/toxins12120753

Summary: Refers to chimeric murine-human mAb cetuximab bound to Streptavidin-ZAP.

See: Yip WL et al. Targeted Delivery and Enhanced Cytotoxicity of Cetuximab-Saporin by Photochemical Internalization in EGFR-Positive Cancer Cells. Mol Pharm 4(2):241-251, 2007.

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

Gick GG, Arora K, Sequeira JM, Nakayama Y, Lai SC, Quadros EV (2020) Cellular uptake of vitamin B12: Role and fate of TCblR/CD320, the transcobalamin receptor. Exp Cell Res 396(1):112256. doi: 10.1016/j.yexcr.2020.112256

Summary: The increased and sustained expression of TCblR in proliferating cells has been used to target toxins preferentially to cancer cells and can be potentially used for targeted delivery of other anti-cancer drugs. In 2010 the authors published a paper which evaluated the potential of using immunotoxins to eliminate cancer cells expressing TCblR the authors performed a series of in vitro experiments using their monoclonal antibody plus Mab-ZAP in varying concentrations. The results indicated that this is a viable therapeutic model that causes minimal peripheral damage.

Related Products: Mab-ZAP (Cat. #IT-04)

London M, Gallo E (2020) The EphA2 and cancer connection: potential for immune-based interventions. Mol Biol Rep 47(10):8037-8048. doi: 10.1007/s11033-020-05767-y

Summary: The authors review the most current mAb-based therapies against EphA2-expressing cancers currently in pre-clinical and/or clinical stages. They reference Sakamoto et al. who performed in vitro testing of two different EphA2 mAbs mixed with Mab-ZAP to discover their therapeutic potential against melanoma.

See: Sakamoto A et al. An Agonistic Antibody to EPHA2 Exhibits Antitumor Effects on Human Melanoma Cells. Anticancer Res 38:3273-3282, 2018.

Related Products: Mab-ZAP (Cat. #IT-04)

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)