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Published on: February 6, 2018
The Development of Monoclonal Antibodies Specific to the Soluble Form of CD155 in the Human Peripheral Blood
Shota Kinoshita1,2, Tomohei Matsuo1,3, Soontae Gwon4
1Department of Immunology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Abstract:
CD155, also known as poliovirus receptor (PVR) or Necl-5, is an immunoreceptor with three immunoglobulin-like domains in the extracellular portion and is ubiquitously expressed on the cell surface of hematopoietic and nonhematopoietic cells. Human CD155 contains membrane-bound CD155 (mCD155) and soluble CD155 (sCD155) lacking the transmembrane region encoded by splicing variants of genes. The serum levels of sCD155 increased in patients with a variety of cancers. Furthermore, sCD155 suppresses tumor immunity through the blockade of DNAM-1 signaling. Therefore, sCD155 is potentially helpful for the diagnosis of cancer development and a novel therapeutic target in cancer treatment. However, monoclonal antibodies (mAbs) specific to sCD155, but not mCD155, have not yet been developed. Here, we generated 14 mAbs (named TX119 to TX122 and TX126 to TX135) that recognize the cytoplasmic region of CD155. These mAbs bind to sCD155, but not mCD155, when applied from the outside of the cell. Moreover, we established the assay system to quantify the sCD155 concentration in human serum. Thus, these mAbs can be utilized for the targeting and quantification of sCD155 in the human peripheral blood.
Insights
Researchers developed novel monoclonal antibodies (mAbs) targeting soluble CD155 (sCD155), a cancer biomarker. These mAbs can quantify sCD155 in serum, aiding cancer diagnosis and treatment strategies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- CD155, also known as poliovirus receptor (PVR) or Necl-5, is an immunoreceptor expressed on cell surfaces.
- Soluble CD155 (sCD155) is found at increased levels in cancer patients and suppresses anti-tumor immunity by blocking DNAM-1 signaling.
- sCD155 shows potential for cancer diagnosis and as a therapeutic target, but specific antibodies for sCD155 were lacking.
Purpose of the Study:
- To develop monoclonal antibodies (mAbs) specifically targeting soluble CD155 (sCD155), not membrane-bound CD155 (mCD155).
- To establish a reliable assay system for quantifying sCD155 concentration in human serum.
- To enable the targeting and quantification of sCD155 in peripheral blood for clinical applications.
Main Methods:
- Generation of 14 unique mAbs (TX119-TX122, TX126-TX135) recognizing the cytoplasmic region of CD155.
- Testing mAb binding specificity to sCD155 versus mCD155 using cell-based assays.
- Development and validation of an assay system for quantifying sCD155 in human serum.
Main Results:
- The generated mAbs specifically bind to sCD155 but not to mCD155 when applied externally.
- The established assay system accurately quantifies sCD155 concentration in human serum.
- These novel mAbs are suitable for targeting and quantifying sCD155 in peripheral blood.
Conclusions:
- Novel mAbs targeting the cytoplasmic region of CD155 have been successfully developed.
- These mAbs demonstrate specificity for sCD155, enabling its detection and quantification.
- The developed mAbs and assay system offer a promising tool for cancer diagnosis and therapeutic strategies targeting sCD155.
