cancer-research

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.

Myers B, Islam S, Gleber Netto FO, Debnath KC, Srivastava S, Xie T, Akhter S, Adebayo AA, Miller J, Lothumalia S, Sathiskumar HN, Amit M (2023) Targeting nociceptive and cholinergic nerves in irradiated oropharyngeal cancer model reveals novel mechanism for dysphagia. Cancer Neuroscience Symposium

Objective: Explore the hypothesis that modulation of cholinergic (CHAT+) and nociceptive (CGRP+) neurons correlate with improved dysphagia.

Summary: Oropharyngeal squamous cell carcinoma is one of the most common types of head and neck cancer. Treatment for OPSCC includes surgery, radiation therapy, chemotherapy, or a combination of therapies. Despite advances in treatment, dysphagia (difficulty swallowing) is still a major burden for patients with OPSCC. The study established a novel murine OPSCC model to explore the role of nerves in dysphagia with cholinergic (CHAT) and nociceptive (CGRP) neurons playing an important role in swallowing outcomes. Targeting CHAT and CGRP could be a novel strategy for OPSCC patients with dysphagia.

Usage: 500 ng of Anti-ChAT-SAP was injected into the trigeminal ganglion in mice.

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Gudgeon J, Marin-Rubio JL, Trost M (2022) The role of macrophage scavenger receptor 1 (MSR1) in inflammatory disorders and cancer. Front Immunol 13:1012002. doi: 10.3389/fimmu.2022.1012002 PMID: 36325338

Objective: Review the role of Macrophage scavenger receptor 1 (MSR1) in health and disease, focusing on the molecular mechanisms influencing expression, its effect on disease process, macrophage function and signaling pathways, and the therapeutic potential of targeting MSR1.

Summary: MSR1 is primarily found on the surface of various types of macrophages and affects processes such as astherosclerosis, innate and adaptive immunity, lung and liver disease and cancer. Recently, MSR1 has been implicated to trigger inflammatory and tumorigenic pathways. MSR1 is most often correlated with the anti-inflammatory M2 macrophage phenotype. Investigations into anti-inflammatory signalling downstream of MSR1 are vital to fully understand the influence of MSR1 expression in inflammatory disease. Manipulating M2 macrophages through MSR1 may represent a new targeted therapeutic approach for diseases such as cancer, arthritis, and other inflammatory diseases.

Usage: In reviewing therapeutic strategies, an antibody-based method was developed using the 2F8 anti-SR-A monoclonal antibody. The antibody conjugated to RAT-ZAP and unconjugated saporin was delivered to mice via intraperitoneal injection to deplete vascular leukocytes (VLCs) from the peritoneum to reduce the tumor burden. 4.8 μg of Rat-ZAP in the absence or presence of 4 μg of clone 2F8 antibody was incubated on ice for 30 min.

Related Products: Rat-ZAP (Cat. #IT-26)

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. doi: 10.1186/s12967-022-03329-3 PMID: 35303878

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