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Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs
Zhao Q, Zong H, Zhu P, Su C, Tang W, Chen Z, Jin S (2024) Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs. Exp Hematol Oncol 13(1):6. doi: 10.1186/s40164-024-00474-x PMID: 38254219
Summary: Cancer immunotherapy has become a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy. Cancer stem cells (CSCs) have the capabilities of self-renewal and differentiation and are also resistant to the traditional therapies of radiotherapy and chemotherapy. The authors review strategies for targeting colorectal CSCs, where one method described uses a biotinylated antibody against EpCAM (clone 3-171) conjugated to saporin via Streptavidin-ZAP (IT-27).
Related Products: Streptavidin-ZAP (Cat. #IT-27)
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Tumor-specific intracellular delivery: peptide-guided transport of a catalytic toxin
Allred CA, Gormley C, Venugopal I, Li S, McGuire MJ, Brown KC (2023) Tumor-specific intracellular delivery: peptide-guided transport of a catalytic toxin. Commun Biol 6(1):60. doi: 10.1038/s42003-022-04385-7 PMID: 36650239
Objective: The demonstration of a peptide optimized by chemical modifications for tumor specificity to deliver saporin, a catalytic toxin, specifically to cancer cells via both in vitro and in vivo.
Summary: Peptides rival antibodies in affinity and specificity and offer an alternative as cancer-targeting molecules. In comparison to antibodies, peptides have a faster development time and lower production cost. The authors isolated peptide MGS4, derived from a phage-displayed library using a non-small cell lung cancer (NSCLC) cell line as the target. MGS4 was modified to identify the minimal binding domain while also improving affinity and stability. Importantly, the authors provide data showing the peptide delivered saporin both in vitro and in vivo to cancer cells demonstrating anti-tumor efficacy in a mouse model.
Usage: In vitro delivery was performed by reacting biotinylated peptide with Streptavidin-ZAP (Cat. #IT-27) in a 1:1 molar ratio. Cells were treated for 6h at 37C. The drug was removed and replaced with media and after 72 hours, cell viability was measured with CellTiter-GLO. In vivo delivery was performed using biotinylated MGS4 reacted with Streptavidin-ZAP and administered via tail-veil injection (7.5 ug/100 ul) 2x/week for 2.5 weeks for a total of 5 treatments.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Intracellular protein delivery: Approaches, challenges, and clinical applications
Chan A, Tsourkas A (2024) Intracellular protein delivery: Approaches, challenges, and clinical applications. BME Frontiers doi: 10.34133/bmef.0035
Objective: To review progress made towards achieving cytosolic delivery of recombinant proteins and possible strategies to enable proteins to cross cell membranes.
Summary: Drug delivery researchers have worked to deliver saporin into tumor cells in the hopes of producing potent next-generation cancer therapeutics. Cationic, anionic, and zwitterionic versions of poly(β-amino ester) have been developed for delivery of saporin. Chemically-modified saporin can be encapsulated by cationic LNPs for in vivo tumor inhibition. Saporin has been used as a model cargo protein for in vivo delivery via fluoropolymer nanoparticles for successful tumor growth inhibition.
Related Products: Saporin (Cat. #PR-01)
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Sensory spinal interoceptive pathways and energy balance regulation
Münzberg H, Berthoud HR, Neuhuber WL (2023) Sensory spinal interoceptive pathways and energy balance regulation. Mol Metab 78:101817. doi: 10.1016/j.molmet.2023.101817 PMID: 37806487
Objective: To review and discuss the roles of spinal sensory pathways, specifically dorsal root ganglia (DRG) afferents, in energy balance regulation, highlighting their contributions to metabolic homeostasis in health and disease.
Summary: This comprehensive review explores the emerging significance of spinal sensory neurons, beyond traditional gut-brain and adipose tissue-to-brain signaling pathways, in regulating energy intake and metabolism. It delves into the anatomy and functions of spinal sensory pathways, emphasizing the potential of DRG afferents in providing metabolic information to the brain. The review suggests that identifying specific DRG neurons and understanding their molecular mechanisms are crucial steps toward developing targeted therapies for metabolic diseases, such as obesity, diabetes, and cancer.
Usage: The publication references that CCK-SAP (IT-31) injected into the nodose ganglia of mice and rats selectively ablates vagal afferent neurons expressing CCKA receptors.
Related Products: CCK-SAP (Cat. #IT-31)
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Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents
Kubeil M, Suzuki Y, Casulli MA, Kamal R, Hashimoto T, Bachmann M, Hayashita T, Stephan H (2023) Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents. Adv Healthc Mater e2301404. doi: 10.1002/adhm.202301404 PMID: 37717209
Summary: This review provides a brief overview of current developments of nanogels in the fields of drug delivery, therapeutic applications, tissue engineering and sensor systems. The authors described one development using saporin. Mimicking the function of molecular chaperones, Kawasaki et al. created magnetic in vivo protein transport nanogels with encapsulated iron oxide nanoparticles. The nanogels also contained saporin, which was rapidly released by an exchange reaction with serum protein. The evaluation using an oral cancer model revealed a reduction in tumor volume and suppression of tumor regrowth, with no change in body weight.
Related Products: Saporin (Cat. #PR-01)
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Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review)
Thongchot S, Aksonnam K, Thuwajit P, Yenchitsomanus PT, Thuwajit C (2023) Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review). Int J Mol Med 52(3):81. doi: 10.3892/ijmm.2023.5284 PMID: 37477132
Objective: The authors review the mechanisms through which the multiple functions of NCL can participate in the progression of cancer. In addition, the studies that define the utility of NCL‑dependent anticancer therapies are summarized, with specific focus being paid to cancer immunotherapeutic approaches.
Summary: NCL is a multifunctional protein abundantly distributed in the nucleus, cytoplasm and cell membrane. It influences carcinogenesis, and the proliferation, survival and metastasis of cancer cells, leading to cancer progression. The overexpression of nucleolin (NCL) in a number of types of cancer provides an attractive antigen target for the development of novel anticancer immunotherapeutic treatments.
Usage: The mice were treated with 0.5 mg/kg body weight of SAP-N6L via intraperitoneal injection.
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Novel approaches towards cancer-directed immune checkpoint inhibition
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)
Pathophysiological roles and applications of glycosphingolipids in the diagnosis and treatment of cancer diseases
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)
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Targeting nociceptive and cholinergic nerves in irradiated oropharyngeal cancer model reveals novel mechanism for dysphagia
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)
The role of macrophage scavenger receptor 1 (MSR1) in inflammatory disorders and cancer
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
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)