Archives in Cancer Research

In recent years, various new drugs such as molecularly targeted drugs and immune checkpoint inhibitors have been released. In such a situation, liquid biopsy is becoming increasingly important as a guide for selecting these new drugs and determining their efficacy. Liquid biopsy is less invasive than conventional tissue biopsy. Because, which uses bodily fluids such as blood or urine enabling frequent biopsies. Therefore, liquid biopsy is considered effective for monitoring of the treatment course. Liquid biopsy has been the subject of research and development in recent years. Liquid biopsy is largely divided into three types one is circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or cell-free DNA (cfDNA), and exosomes. In this short communication, we focus only on Circulating tumor cells (CTCs). It is known that a trace amount of cells derived from cancer tissue infiltrate blood and lymph fluid and circulate in the body of cancer patients. Those cells are called circulating tumor cells (CTCs). CTC has been the subject of research and development throughout the world in recent years. Many of the CTC identification methods, used over 20 years ago were based on polymerase chain reaction (PCR) and were problematic in their sensitivity and reproducibility. One of the many CTC identification methods developed after the PCR-based methods, the Cell Search System (Veridex, USA) established by Cristofanilli et al. using automated immunostaining, was based on direct observation of CTCs under a fluorescent microscope, and was anticipated to be a new cancer biomarker. The Cell Search System obtained U.S. This method depends on the EpCAM antigen expressed on the CTC surface. However, not all CTCs express EpCAM antigen on its surface. So, such CTCs can‘t be captured by this system. In the present review, we focus on the newly developed our new technology for capturing renal cell cancer CTC(RCC-CTC) with RCC specific antibody combined with new devices. We believe that the technology we developed will be useful for judgment of treatment efficacy and drug selection for the treatment of renal cell cancer. It has been reported that G250 antigen is expressed on the surface of RCC cells. Also, it is reported to be particularly high expressed in clear cell type RCC(CRCC). Conveniently, 70～80％ of RCC are CRCC pathologically. Therefore, we devised the development of a new method for identifying CRCC-CTC targeting G250 antigen. CTCs are extremely rare cells and are present in numerous number of PBMCs (Peripheral Blood Mononuclear Cells). Therefore, an important step in CTC identification is to remove as much PBMCs as possible. We use CelSee to eliminate PBMCs. CelSee is a micro fluidic device method, a device that was awarded The Scientist's annual Top 10 Innovations of 2015. The CTC and the leukocyte deformability are greatly different, and the CTC is captured based on the difference between CTC and diameters of PBMCs. PBMCs can pass through even if the deformation characteristics are large and larger than the Pore channel, but CTC can’t pass through due to its small deformation characteristics. The micro fluidic chip method was designed based on this principle. The sensitivity of the our proposed method for eliminating PBMCs by CelSee combined with identifying CRCC-CTC targeting the G250 antigen is extremely high, and we have obtained an EU patent for this technology. The capturing rate of CRCC-CTC by our new technology exceeded 90%. Currently, clinical research using our technology is about to begin. If the clinical research proves the usefulness of our technology, we believe that it will contribute greatly to the treatment of kidney cancer without biomarker, although there are various drug options.