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Oncotarget | In vitro studies on CNGRC-CPG2 fusion proteins for ligand-directed enzyme prodrug therapy for targeted cancer therapy


Oncotarget Volume 11, Issue 6 reported in a recent research paper that in vitro binding assays of the purified constructs showed that both X-CPG2 and X-CPG2-X bound with high affinity to cancer cells expressing high levels of APN, compared to their binding to cells expressing low levels of APN. Further in vitro studies of the constructs to assess the therapeutic potential of LDEPT were carried out using cells expressing high and low levels of APN.

Dr. Sayed K. Goda from the Cairo University, Faculty of Science, Chemistry Department in Giza Egypt said, "Metastasis is a key problem preventing cancer treatment, and often results in patient death."

"Metastasis is a key problem preventing cancer treatment, and often results in patient death."

- Dr. Sayed K. Goda, Cairo University, Faculty of Science, Chemistry Department

Several studies have reported that various types of cancer cells have abnormally high levels of expression of APN, which made it a promising target for cancer therapy.

Thus, the CNGRC peptide has been utilized as a carrier for many cancer-related applications, such as cancer cell imaging, and the development of novel anti-cancer compounds that could be targeted to tumor cells.

In the LDEPT strategy, a protein or peptide ligand is used to direct the enzyme to the tumor site where the prodrug will be converted to cytotoxic drug resulting in cancer cell death.

Figure 1: Schematic representation of the Ligand-Directed Enzyme Pro-Drug Therapy (LDEPT) strategy. Tumor cells that express cancer specific receptors (such as aminopeptidase N "APN") are bound via a specific ligand (such as CNGRC) that is attached via a linker to a therapeutic enzyme (such as CPG2) that can convert an inactive pro-drug (ZD2767P) to a cytotoxic compound at the site of tumor cells.

In this study, they used two derivatives containing a cyclic peptide that binds with high affinity to APN and direct CPG2 to tumor cells.

They investigated the specific binding of the fusion proteins using cancer cell lines with different levels of APN expression.

The Goda Research Team concluded in their Oncotarget Research Paper, that they exposed APN expressing cancer cells, pre-treated with the fusion proteins or with controls, to the prodrug, ZD2767P.

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Full text - https://doi.org/10.18632/oncotarget.27478

Correspondence to - Sayed K. Goda - skgoda@outlook.com

Keywords - targeted cancer therapy, carboxypeptidase G2, glucarpidase, ligand directed enzyme prodrug therapy, antibody directed enzyme prodrug therapy

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