cancer-research

Lee W, Song G, Bae H (2022) Laminarin attenuates ros-mediated cell migration and invasiveness through mitochondrial dysfunction in pancreatic cancer cells. Antioxidants (Basel) 11(9):1714. doi: 10.3390/antiox11091714 PMID: 36139787

Objective: To determine the effects of laminarin on pancreatic cancer.

Summary: Laminarin showed synergistic effects when combined with 5-FU, a standard anticancer agent for pancreatic ductal adenocarcinoma (PDAC) with potential as a treatment for PDAC.

Usage: Lund et al. work on 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin Anti-CD105-SAP.

Related Products: Anti-CD105-SAP (Cat. #IT-80)

See Also:

• Lund K et al. 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. J Exp Clin Cancer Res 36(1):185, 2017.

Ardini M, Vago R, Fabbrini MS, Ippoliti R (2022) From immunotoxins to suicide toxin delivery approaches: Is there a clinical opportunity?. Toxins (Basel) 14(9):579. doi: 10.3390/toxins14090579 PMID: 36136517

Objective: To give an overview describing some of the bacterial and plant enzymes studied so far for their delivery and controlled expression in tumor models.

Summary: “Suicide gene” therapy (SGT), consists of the selective delivery of genes coding for toxic proteins, into target cancer cells. This new and promising approach may overcome some of the issues related to the use of chemical agents (chemotherapy) such as as specificity, high dosages with accompanying side effects, and chemoresistance induction.

Takahashi JI, Nakamura S, Onuma I, Zhou Y, Yokoyama S, Sakurai H (2022) Synchronous intracellular delivery of EGFR-targeted antibody-drug conjugates by p38-mediated non-canonical endocytosis. Sci Rep 12(1):11561. doi: 10.1038/s41598-022-15838-8 PMID: 35798841

Objective: The binding of cetuximab to EGFR suppresses ligand-induced signaling events. The authors demonstrate that synchronous non-canonical EGFR endocytosis can increase the efficacy of EGFR-targeting ADCs.

Summary: Epidermal growth factor (EGFR) has been a popular target in the treatment of cancer via monoclonal antibodies, specifically cetuximab and panitumumab. They have been applied to antibody-drug conjugates (ADCs) and their clinical efficacy had been demonstrated, but this efficacy has also been limited by acquired resistance via secondary mutations or the activation of bypass pathways. To overcome these limiting factors, the authors investigated if non-canonical clathrin-mediated endocytosis (CME) of EGFR induced the internalization of membrane-bound EGFR-targeted mAbs. Their results show that tumor necrosis factor-alpha strongly induces endocytosis of the cetuximab-EGFR complex via the p38 phosphorylation of EGFR and that Hum-ZAP, a secondary antibody conjugated to saporin, will also undergo internalization with the complex and enhance anti-proliferative activity.

Related Products: Hum-ZAP (Cat. #IT-22)

Zhai BT, Tian H, Sun J, Zou JB, Zhang XF, Cheng JX, Shi YJ, Fan Y, Guo DY (2022) Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer. J Translational Medicine 20:135.

Summary: The authors describe how a conjugate of Saporin and ATF (Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer amino‐terminal fragment of urokinase) exerts antitumor effects by targeting Urokinase-type plasminogen activator receptor (uPAR).

Napoli M, Wu SJ, Gore BL, Abbas HA, Lee K, Checker R, Dhar S, Rajapakshe K, Tan AC, Lee MG, Coarfa C, Flores ER (2022) ΔNp63 regulates a common landscape of enhancer associated genes in non-small cell lung cancer. Nat Commun 13(1):614. doi: 10.1038/s41467-022-28202-1 PMID: 35105868

Objective: To investigate the underlying mechanistic role regulated by ΔNp63 in lung cancer development.

Summary: Use of a ΔNp63-specific conditional knockout mouse model and xenograft models of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results show that ΔNp63 promotes non-small cell lung cancer by maintaining the lung stem cells necessary for lung cancer cell initiation and progression in quiescence. ΔNp63 regulates enhancers of cell identity genes.

Usage: Immunofluorescence and IHC (1:100)

Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

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.

Polito L (2022) Antibody based delivery of toxins and other active molecules for cancer therapy. Biomedicines 10(2):267. doi: 10.3390/biomedicines10020267 PMID: 35203476

Summary: This introduction to studies collected in a special issue that confirmed the potential of immunotherapy for targeted therapy in different cancer models. In the near future, antibody-based therapeutic approaches could improve the outcomes of cancer patients, overcoming some difficulties associated with standard therapy.

Biomedicines, Volume 10, Issue 2 (February 2022) – 318 articles

Shramm PA, Ancheta LR, Bouajram R, Lappi DA (2021) A brief history of saporin and its contributions to neuroscience. Neuroscience 2021 Abstracts J002.11. Society for Neuroscience, Virtual.

Summary: When investigating the origins of targeted toxins (a drug, therapy, or scientific tool directed to a unique extracellular target), an appropriate place to begin is with the Nobel Prize-winning work of Paul Ehrlich and his concept of the “magic bullet.” Over 100 years later, the use of targeted toxins to perform molecular neurosurgery has become a vital practice that allows researchers to observe changes in organisms after eliminating a neuronal population. A prime example of this practice is the specific targeting of cholinergic neurons in the basal forebrain to mimic Alzheimer’s disease (AD). The research tool designed for this purpose is 192-IgG-Saporin, an antibody conjugated to the ribosome-inactivating protein (RIP) Saporin. Researchers have used this targeted toxin for over 30 years. A 2019 publication by Verkhratsky et al. reviews AD models and states this is the only lesion model that specifically targets cholinergic neurons. In 1983, during a quest to find the optimal payload for a targeted toxin, Fiorenzo Stirpe and colleagues discovered Saporin, a plant protein isolated from the common soapwort plant Saponaria officinalis. Unlike ricin and abrin, Saporin does not have a binding chain and cannot enter a cell on its own. Scientists have devised new ways to use Saporin to advance their research and drug development activities. Just a few examples include: 1. A novel suicide gene therapy approach that uses a vector encoding a double-stranded DNA aptamer to deliver the gene encoding Saporin, 2. Delivery of Saporin encapsulated in a nanotechnology system for development of cancer treatments, 3. A deeper understanding of the difference between pain and itch and the relevant pathways, and 4. Development of a stable epilepsy animal model that is used for screening specific treatments that will lead to micro-methods to eliminate the disease. This review will focus on Saporin as the payload delivered to cells. Targeted toxins (typically targeted by an antibody or peptide chemically linked or genetically fused) provide robust tools for neuroscience where ablation of specific neuronal populations is used to study behavior and function. Saporin is an ideal molecule because of its extreme resistance to high temperatures and denaturation, retention of catalytic activity after conjugation, and lack of a binding chain to allow entrance to the cytoplasm of cells on its own. As a result, it is one of the most studied RIPs used for its vigorousness, potency, safety, and ease of use in the laboratory. The information presented will shed light on the history of Saporin, current applications, and what the future holds for this protein in the neuroscience field.

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

View the complete poster.

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.