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.
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.
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).
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.
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.
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.
Hoffmann RM, Mele S, Cheung A, Larcombe-Young D, Bucaite G, Sachouli E, Zlatareva I, Morad HOJ, Marlow R, McDonnell JM, Figini M, Lacy KE, Tutt AJN, Spicer JF, Thurston DE, Karagiannis SN, Crescioli S (2020) Rapid conjugation of antibodies to toxins to select candidates for the development of anticancer antibody-drug conjugates (ADCs). Sci Rep 10(1):8869. doi: 10.1038/s41598-020-65860-x
Objective: To facilitate rapid and cost-effective screening of antibody and toxin combinations for activity and safety, based on streptavidin-biotin conjugation
Summary: For antibody selection, the authors evaluated internalization by target cells using streptavidin-linked antibodies conjugated to biotinylated saporin, a toxin unable to cross cell membranes. For payload selection, the authors biotinylated toxins and conjugated them to antibodies linked to streptavidin to evaluate antitumour activity and pre-clinical safety.
Usage: Streptavidin-linked antibody was incubated for 30min with biotinylated Saporin (BT-ZAP) at a molar ratio of 1:6.
Komatsu N, Komatsu M, Ohashi R, Horii A, Hoshi K, Takato T, Abe T, Hamakubo T (2020) Saponin facilitates anti-robo1 immunotoxin cytotoxic effects on maxillary sinus squamous cell carcinoma. J Oncol 2020:9593516. doi: 10.1155/2020/9593516 PMID: 32256588
Objective: To examine whether a flashed treatment with saponin exerted a significant specific cytotoxic effect on cancer cells.
Summary: The authors have shown previously the enhanced cytotoxic effects of saporin-conjugated anti-Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. The combination of an immunotoxin with saponin also exhibited a significant tumor-suppressive effect on mice HSQ-19 xenograft.
Usage: A saporin-conjugated anti-Robo1 antibody (IT-Robo1) and saporin-conjugated negative control antibody (IT-NC), were prepared by incubating 121μl of 1.1μM streptavidin-saporin and 138μl of 1.1μM biotinylated monoclonal antibodies for 30 min at room temperature. HSQ-89 cells were seeded at 2.0×104cells per well in 96-well plates and cultured overnight. On the following day, they were exposed to various concentrations (0.054 pM∼4.2 nM) of either IT-Robo1 or IT-NC.
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.
