References

Marquez J (2023) PTGFRN as a target for antibody-drug conjugate (ADC) development in mesothelioma and medulloblastoma. Univ Maryland Baltimore Thesis.

Objective: To investigate the role of Prostaglandin F2 Receptor Negative (PTGFRN) regulator in cancer progression and develop an antibody-drug conjugate (ADC) targeting PTGFRN for the treatment of mesothelioma and pediatric medulloblastoma.

Summary: This dissertation explores the expression and function of PTGFRN in mesothelioma and pediatric medulloblastoma, identifying its association with aggressive cancer phenotypes. The study further develops a potent ADC using a PTGFRN-specific monoclonal antibody conjugated to the cytotoxic compound Duocarmycin, demonstrating significant anti-cancer efficacy in both in vitro and in vivo models .

Usage: Both a custom direct conjugate and Fab-ZAP Mouse (IT-48) were used (up to 10 nM) on transfected HEK-293A cells.

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

Metz M, Kolkhir P, Altrichter S, Siebenhaar F, Levi-Schaffer F, Youngblood BA, Church MK, Maurer M (2023) Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases. Allergy doi: 10.1111/all.15850 PMID: 37605867

Objective: Authors review the role of mast cells (MC) in the pathogenesis of chronic urticaria (CU), explore current therapeutic strategies, and introduce the concept of MC silencing as a strategy to block activation of MCs without eliciting immunosuppressive adverse effects.

Summary: CU is a MC-dependent disease with limited therapeutic options. Current strategies are directed at inhibiting IgE-mediated activation of MCs. MC depletion or silencing strategies are being developed to overcome limitations of singularly targeted agents. MC silencers, such as monoclonal antibodies that engage inhibitory receptor like sialic acid-binding immunoglobulin-like lectin8 (Siglec-8) have reached preclinical stages of development. Siglecs have been shown to be internalized upon antibody engagement, such as Siglec-8, and is being used to deplete MCs via conjugating saporin to the internalizing Siglec-8 antibody to cause cell death in human mast cells.

Usage: Usage: Anti-Siglec-8 (2C4)-SAP was used at 2.5 µg/ml to eliminate eosinophils and at 1.25 µg/ml to eliminate the HMC-1.2 human mast cell line.

Related Products: Saporin (Cat. #PR-01)

See Also:

• O’Sullivan J et al. Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells. J Allergy Clin Immunol 141:1774-1785.e1777, 2018.

Dobryakova YV, Gerasimov K, Spivak YS, Korotkova T, Koryagina A, Deryabina A, Markevich VA, Bolshakov AP (2023) The induction of long-term potentiation by medial septum activation under urethane anesthesia can alter gene expression in the hippocampus. Int J Mol Sci 24(16):12970. doi: 10.3390/ijms241612970 PMID: 37629149

Objective: To study changes in the expression of early genes in hippocampal cells in response to stimulation of the dorsal medial septal area (dMSA), leading to long-term potentiation in the hippocampus.

Summary: The data suggest that the induction of long-term potentiation by dMSA activation enhances the expression of select early genes in the hippocampus.

Usage: Injection into the medial septum area (MSA) at a rate of 0.2μL/min. The drug was infused at a concentration of 1.5μg/per rat.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Wang C, Pan C, Yong H, Wang F, Bo T, Zhao Y, Ma B, He W, Li M (2023) Emerging non-viral vectors for gene delivery. J Nanobiotechnology 21(1):272. doi: 10.1186/s12951-023-02044-5 PMID: 37592351

Summary: This review describes the fastest-growing and efficient non-viral gene delivery vectors that include liposomes and lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). One group designed and synthesized HPAEs with positive and negative charges to deliver saporin. Another group performed cell experiments that demonstrated that a boronic acid-grafted dendrimer vector had good delivery ability for saporin.

Related Products: Saporin (Cat. #PR-01)

Liu X, Si W, Zhao Z, Liu N, Yang Q, Zhou R, Zhu R, Duan S, CHen Y, Yin L (2023) Engineering blood-brain barrier-permeable and tumor cell-ingestible pro-proteins for glioblastoma treatment. Sci China Chem doi: 10.1007/s11426-023-1684-5

Objective: Using M2-D, a blood brain penetrating pro-protein, conjugated to saporin to kill glioblastoma cells in mice.

Summary: M2-D, a blood brain penetrating pro-protein, is conjugated to saporin allowing the cytotoxicity of saporin to reach through the brain in a L-type amino acid transport mediated delivery. M2D-Saporin demonstrated selective killing of glioblastoma cells in mice and didn’t exhibit general systemic toxicity.

Usage: Cy5-Saporin or Cy5-saporin-M2-D was i.v. injected to BALB/c mice at 0.5 mg Cy5-saporin/kg

Related Products: Saporin (Cat. #PR-01)

Miles AJ, Drew ED, Wallace BA (2023) DichroIDP: a method for analyses of intrinsically disordered proteins using circular dichroism spectroscopy. Commun Biol 6(1):823. doi: 10.1038/s42003-023-05178-2 PMID: 37553525

Objective: To use DichroIDP software to analyze secondary structures of proteins containing disordered structures via circular dichroism spectroscopy.

Summary: Globular proteins have specific shapes and mainly contain standard secondary structures. In contrast, intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) have flexible chains with limited persistent secondary structures.

Usage: Saporin is used to study secondary and tertiary protein structure

Related Products: Saporin (Cat. #PR-01)

Ploeg E (2023) Novel approaches towards cancer-directed immune checkpoint inhibition. Univ Groningen Thesis. doi: 10.33612/diss.737906343

Objective: To evaluate a novel bispecific antibody, bsAb CD73xEGFR, that inhibits the immunosuppressive enzyme CD73 on cancer cells in an EGFR-directed manner.

Summary: The researchers constructed a bispecific antibody, bsAb CD73xEGFR, that binds to both CD73 and EGFR on cancer cells. In preclinical studies, they found that bsAb CD73xEGFR was more effective than the monospecific anti-CD73 antibody oleclumab at reducing tumor growth and enhancing anti-tumor immune responses, likely due to its ability to direct CD73 inhibition specifically to cancer cells overexpressing EGFR.

Usage: Cancer cells were incubated with bsAb CD73xEGFR (1 μg/ml) (or controls) in the presence of Fab-ZAP human (Cat. #IT-51). Apoptotic cancer cell death was evaluated after 24 h by flow cytometry using Annexin-V/PI staining.

Related Products: Fab-ZAP human (Cat. #IT-51)

Jorgensen MD (2023) Designing coiled-coil peptide materials for biomedical applications. Purdue University Thesis.

Objective: Using saporin [PR-01] containing hydrogel to target and eliminate cancer cells.

Summary: Hydrogels can bind molecular cargo and be used to shuttle cytotoxic drugs across the body. Using a pH-responsive hyaluronic acid nanogel containing saporin, cancer cells with overexpressed CD44 receptor are eliminated.

Related Products: Saporin (Cat. #PR-01), Anti-CD44-SAP (Cat. #IT-72)

See Also:

• Ding L, Jiang Y, Zhang J, Klok HA, Zhong Z (2018) pH-Sensitive Coiled-Coil Peptide-Cross-Linked Hyaluronic Acid Nanogels: Synthesis and Targeted Intracellular Protein Delivery to CD44 Positive Cancer Cells. Biomacromolecules 19(2):555-562. doi: 10.1021/acs.biomac.7b01664 PMID: 29284258

Jin X, Yang GY (2023) Pathophysiological roles and applications of glycosphingolipids in the diagnosis and treatment of cancer diseases. Prog Lipid Res 101241. doi: 10.1016/j.plipres.2023.101241 PMID: 37524133

Objective: The authors review the tumor-related biological functions of GSLs and recent progress in using GSLs and related enzymes to diagnose and treat tumor diseases.

Summary: Glycosphingolipids (GSLs) are glycolipids present on the surface of living cell membranes. Specific GSLs and related enzymes are abnormally expressed in many cancer diseases and affect the malignant characteristics of tumors. The regulatory roles of GSLs in signaling pathways suggest that they are involved in tumor pathogenesis. GSLs have therefore been widely studied as diagnostic markers of cancer diseases and important targets of immunotherapy.

Usage: The stage-specific embryonic antigen-4 (SSEA4) mAb, MC-813-70, was mixed with Mab-ZAP at a molar ratio of approximately 3:1 with the complex used at nanomolar concentrations on MDA-MB-231 cells, a triple negative breast cancer cell known to express SSEA-4. The conjugate was able to reduce tumor viability in vitro.

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

See Also:

• Ruggiero FM et al. Exploiting the internalization feature of an antibody against the glycosphingolipid SSEA-4 to deliver immunotoxins in breast cancer cells. Immunol Cell Biol 98(3):187-202, 2020.

Zhang H, Zhu Y, Chen S, Deng K, Zheng M, Zeng Z, Wang Q, Cai H, Lu Z (2023) Autonomic nerve and its modulation approaches for heart failure. Brain & Heart 1(2):0913. doi: 10.36922/bh.0913

Objective: Authors review neural modulation approaches that can assist in the management of heart failure.

Summary: The autonomic nervous system governs the heart’s neurological regulation through opposing functions of its sympathetic and parasympathetic components. Potential treatments for heart failure include inhibiting the sympathetic nerve’s overactivity and restoring parasympathetic activity in the heart. CTB-SAP was used to ablate cardiac sympathetic neurons via retrograde transport on stellate ganglion neurons.

Usage: CTB-SAP was injected into the right superior vervical ganglion of adult male Sprague-Dawley rats (50 ug/rat).

Related Products: CTB-SAP (Cat. #IT-14)

See Also:

• Llewellyn-Smith IJ et al. Retrogradely transported CTB-saporin kills sympathetic preganglionic neurons. Neuroreport 10(2):307-312, 1999.