GUCY2C Specific Neutra™ Antibody Products

Guanylyl cyclase C (GUCY2C), also known as GC-C or STaR, is a type I transmembrane protein with a molecular weight of approximately 120 kDa, which belongs to the guanylyl cyclase receptor family. GUCY2C functions as a receptor for endogenous guanylin and uroguanylin, as well as for exogenous heat-stable enterotoxin, with expression primarily in intestinal crypts and villus cells. Upon ligand binding to the extracellular domain, GUCY2C is activated and triggers downstream signaling pathways to regulate intestinal homeostasis and tumorigenesis.

Its Gene ID: 2984, UniProtKB ID: 601330, and OMIM ID: 601330.

GUCY2C-Cyclic Guanosine Monophosphate (cGMP) Signaling Axis

GUCY2C-cGMP signaling plays a crucial role in regulating intra- and extracellular ion concentrations and intestinal water-electrolyte balance, maintaining intestinal function, and protecting the integrity of the intestinal barrier. Activation of GUCY2C by ligands leads to the production of cGMP, which further controls cellular functions through cation channel proteins, phosphodiesterase (PDE), and cGMP-dependent protein kinase II (PKGII). Abnormal expression of GUCY2C in the absence of ligand stimulation can disrupt colorectal epithelial cell homeostasis, potentially leading to intestinal tumorigenesis by affecting the integrity of the intestinal barrier formed by epithelial cell junctions.

Fig.1 The GUCY2C-cGMP signaling axis and intestinal fluid secretion.^1,3

Therapeutic Strategies for Targeting GUCY2C

GUCY2C is densely distributed in the intestine and overexpressed in colorectal cancer cells. Its ability to identify and target cancer cells for immunotherapy treatment renders it a valuable biomarker.

Fig.2 The primary modalities for GUCY2C-directed cancer immunotherapy.^2,3

• GUCY2C Vaccines

An adenovirus-based vaccine has been developed for GUCY2C delivery, aimed at stimulating CD8+ T cells to trigger an immune response and hinder colorectal cancer metastasis.

• GUCY2C Bispecific Antibodies

A promising approach to cancer therapy is the recruitment of cytotoxic T lymphocytes to tumor cells expressing target antigens by T-cell engaging bispecific Antibodies. A good example is a bispecific antibody with an anti-GUCY2C arm and an anti-CD3 arm. It has been developed as a biotherapeutic agent for colorectal cancer and has shown promising efficacy in other gastrointestinal malignancies.

• GUCY2C Immunotoxins

Antibody-drug conjugates (ADCs) targeting GUCY2C have been investigated for the treatment of colorectal cancer. By specifically targeting the GUCY2C receptor, these ADCs can deliver cytotoxic agents directly to cancer cells, minimizing off-target effects and improving therapeutic efficacy.

• GUCY2C Chimeric Antigen Receptor (CAR)-T Cells

The unique localization of GUCY2C expression in the intestine, distinct from the systemic immune system, presents an ideal target for CAR-T cell therapy in treating tumors. Preclinical studies have shown that GUCY2C CAR-T therapy is effective in inhibiting tumor growth, particularly against colorectal cancer transferred to the lungs. Importantly, this therapy does not cause autoimmune tissue damage, highlighting its potential as a safe and effective treatment option.

Creative Biolabs offers multiple recombinant anti-GUCY2C antibody products for ELISA, FC, IHC, and WB. Customization of GUCY2C-based neutralizing antibodies and functional antibodies is also available for you here.

REFERENCES

1. Rappaport, Jeffrey A., and Scott A. Waldman. "The guanylate cyclase C—cGMP signaling axis opposes intestinal epithelial injury and neoplasia." Frontiers in oncology 8 (2018): 299.
2. Baybutt, Trevor R., Allison A. Aka, and Adam E. Snook. "The heat-stable enterotoxin receptor, guanylyl cyclase C, as a pharmacological target in colorectal cancer immunotherapy: a bench-to-bedside current report." Toxins 9.9 (2017): 282.
3. Distributed under open access license CC BY 4.0, without modification.