Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 18 November 2022
Okayama University research: Track changes: A new test to study cancer progression

(Okayama, 18 November) In a study recently published in Frontiers in Oncology, researchers from Okayama University develop a laboratory test to monitor the progression of cancer.

The immune system fights cancer cells in various ways. Real time information about the ‘fight-situation’ in cancer could potentially be used as a prediction/evaluation tool in cancer care. When immune cells attack cancer cells, cancer cell-specific proteins (known as cancer antigens) are released from killed cancer cells, producing antibodies against cancer antigens. Thus, the antibodies in a patient’s blood function as an indicator of the level of antitumor response. However, quantitatively measuring antibodies comprehensively has been challenging in laboratories because cancer antigens are unstable and aggregate. A research team led by Professor FUTAMI Junichiro and MIYAMOTO Ai (graduate student) at Okayama University has developed an assay that makes antibody testing more accessible.

Cancer/testis antigens (CTAs) are one of the main antigens expressed in cancer cells and show different expression patterns in cancer patients. A diagnostic test requires various CTAs array sets to detect antibodies related to antitumor immune reactions. The preparation of sets of aggregative and unstable CTAs and the construction of a validated assay system are needed for clinical applications.

To overcome this issue, the researchers used chemically modified CTA molecules. When CTA molecules were chemically modified with a cationic charge to sulfur-containing groups, they showed water-solubility and ensured all regions of the molecule were exposed. These modified CTA molecules were then conjugated onto chemical beads creating the ‘MUSCAT’ system.

The team first established the so-called MUSCAT’s methodology for confirming the sensitivity, specificity, and accuracy using ‘positive controls’. These control antibodies were produced in rabbits by the administration of modified CTAs. Antibodies were then purified from the rabbit blood and served to validate the MUSCAT system. These antibodies are also available for biochemical research to detect the endogenous CTAs expressed in cancer-derived cell-lines.

To clinically test the system, the researchers used samples from prostate cancer patients. The patients were enrolled in a successful clinical trial for an experimental gene therapy, resulting in complete tumor regression. When the antibodies from patient’s blood were tested on the MUSCAT system, the quantities of antibodies found were closely related to the shrinkage of tumors. The MUSCAT system could therefore be used to monitor the effectiveness of cancer treatment.

Background
Cancer/testis antigens: Cancer/testis antigens (CTAs) are the main class of antigens found on most types of tumors and restricted expression in normal tissues. During the immune system attacks on cancer cell, CTAs released from killed cancer cells stimulate anti-CTAs antibody production due to their immunogenicity. The level of anti-CTAs antibodies reflects the antitumor reaction and potential for immunotherapy.

With time, tumors develop techniques to evade the immune system. Immunotherapy, a form of cancer therapy, focuses on reigniting the immune system in such cases. Hence, measuring the reactivation of the immune response by means of antibody testing is an indispensable tool to check the effectiveness of immunotherapy. Assays that measure the antibody response are useful for monitoring the stages of cancer, repression of the immune system, or activation of the immune system after immunotherapy.

Reference
Ai Miyamoto, Tomoko Honjo, Mirei Masui, Rie Kinoshita, Hiromi Kumon, Kazuhiro Kakimi, Junichiro Futami. Engineering cancer/testis antigens with reversible S-cationization to evaluate antigen spreading. Frontiers in Oncology, 2022 May 4;12:869393.
DOI：10.3389/fonc.2022.869393.
https://www.frontiersin.org/articles/10.3389/fonc.2022.869393/full

Correspondence to
Professor Futami Junichiro, Ph.D.
Medical Protein Engineering Laboratory,
Graduate School for Interdisciplinary Science and Engineering in Health Systems,
Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
E-mail: futamij (a) okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @
https://www.okayama-u.ac.jp/user/proteng/

Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku , Okayama 700-8530, Japan
Public Relations Division
E-mail: www-adm(a) adm.okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
Website: //www.okayama-u.ac.jp/index_e.html
Okayama Univ. e-Bulletin: //www.okayama-u.ac.jp/user/kouhou/ebulletin/
We love OKAYAMA UNIVERSITY: https://www.youtube.com/watch?v=7cXlttQIk3E
Okayama University Image Movie（2020）
https://www.youtube.com/watch?v=BKRoF0tffmA
Okayama University supports the Sustainable Development Goals: https://sdgs.okayama-u.ac.jp/en/

Okayama University Medical Research Updates （OU-MRU）
The whole volume : OU-MRU (1- )
Vol.1：Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2：Ensuring a cool recovery from cardiac arrest
Vol.3：Organ regeneration research leaps forward
Vol.4：Cardiac mechanosensitive integrator
Vol.5：Cell injections get to the heart of congenital defects
Vol.6：Fourth key molecule identified in bone development
Vol.7：Anticancer virus solution provides an alternative to surgery
Vol.8：Light-responsive dye stimulates sight in genetically blind patients
Vol.9：Diabetes drug helps towards immunity against cancer
Vol.10：Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11：Compound-protein combination shows promise for arthritis treatment
Vol.12：Molecular features of the circadian clock system in fruit flies
Vol.13：Peptide directs artificial tissue growth
Vol.14：Simplified boron compound may treat brain tumours
Vol.15：Metamaterial absorbers for infrared inspection technologies
Vol.16：Epigenetics research traces how crickets restore lost limbs
Vol.17：Cell research shows pathway for suppressing hepatitis B virus
Vol.18：Therapeutic protein targets liver disease
Vol.19：Study links signalling protein to osteoarthritis
Vol.20：Lack of enzyme promotes fatty liver disease in thin patients
Vol.21：Combined gene transduction and light therapy targets gastric cancer
Vol.22：Medical supportive device for hemodialysis catheter puncture
Vol.23：Development of low cost oral inactivated vaccines for dysentery
Vol.24：Sticky molecules to tackle obesity and diabetes
Vol.25：Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26：Protein for preventing heart failure
Vol.27：Keeping cells in shape to fight sepsis
Vol.28：Viral-based therapy for bone cancer
Vol.29：Photoreactive compound allows protein synthesis control with light
Vol.30：Cancer stem cells’ role in tumor growth revealed
Vol.31：Prevention of RNA virus replication
Vol.32：Enzyme target for slowing bladder cancer invasion
Vol.33：Attacking tumors from the inside
Vol.34：Novel mouse model for studying pancreatic cancer
Vol.35：Potential cause of Lafora disease revealed
Vol.36：Overloading of protein localization triggers cellular defects
Vol.37：Protein dosage compensation mechanism unravelled
Vol.38：Bioengineered tooth restoration in a large mammal
Vol.39：Successful test of retinal prosthesis implanted in rats
Vol.40：Antibodies prolong seizure latency in epileptic mice
Vol.41：Inorganic biomaterials for soft-tissue adhesion
Vol.42：Potential drug for treating chronic pain with few side effects
Vol.43：Potential origin of cancer-associated cells revealed
Vol.44：Protection from plant extracts
Vol.45：Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46：New method for suppressing lung cancer oncogene
Vol.47：Candidate genes for eye misalignment identified
Vol.48：Nanotechnology-based approach to cancer virotherapy
Vol.49：Cell membrane as material for bone formation
Vol.50：Iron removal as a potential cancer therapy
Vol.51：Potential of 3D nanoenvironments for experimental cancer
Vol.52：A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53：Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54：Measuring ion concentration in solutions for clinical and environmental research
Vol.55：Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56：New device for assisting accurate hemodialysis catheter placement
Vol.57：Possible link between excess chewing muscle activity and dental disease
Vol.58：Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59：Role of commensal flora in periodontal immune response investigated
Vol.60：Role of commensal microbiota in bone remodeling
Vol.61：Mechanical stress affects normal bone development
Vol.62：3D tissue model offers insights into treating pancreatic cancer
Vol.63：Promising biomarker for vascular disease relapse revealed
Vol.64：Inflammation in the brain enhances the side-effects of hypnotic medication
Vol.65：Game changer: How do bacteria play Tag ?
Vol.66：Is too much protein a bad thing?
Vol.67：Technology to rapidly detect cancer markers for cancer diagnosis
Vol.68：Improving the diagnosis of pancreatic cancer
Vol.69：Early gastric cancer endoscopic diagnosis system using artificial intelligence
Vol.70：Prosthetics for Retinal Stimulation
Vol.71：The nervous system can contribute to breast cancer progression
Vol.72：Synthetic compound provides fast screening for potential drugs
Vol.73：Primary intraocular lymphoma does not always spread to the central nervous system
Vol.74：Rising from the ashes—dead brain cells can be regenerated after traumatic injury
Vol.75：More than just daily supplements — herbal medicines can treat stomach disorders
Vol.76：The molecular pathogenesis of muscular dystrophy-associated cardiomyopathy
Vol.77：Green leafy vegetables contain a compound which can fight cancer cells
Vol.78：Disrupting blood supply to tumors as a new strategy to treat oral cancer
Vol.79：Novel blood-based markers to detect Alzheimer’s disease
Vol.80：A novel 3D cell culture model sheds light on the mechanisms driving fibrosis in pancreatic cancer
Vol.81：Innovative method for determining carcinogenicity of chemicals using iPS cells
Vol.82：Making memories — the workings of a neuron revealed
Vol.83：Skipping a beat — a novel method to study heart attacks
Vol.84：Friend to Foe—When Harmless Bacteria Turn Toxic
Vol.85：Promising imaging method for the early detection of dental caries
Vol.86：Plates and belts — a toolkit to prevent accidental falls during invasive vascular proceduresa
Vol.87：Therapeutic potential of stem cells for treating neurodegenerative disease
Vol.88：Nanotechnology for making cancer drugs more accessible to the brain
Vol.89：Studying Parkinson’s disease with face-recognition software
Vol.90：High levels of television exposure affect visual acuity in children
Vol.91：Meeting high demand: Increasing the efficiency of antiviral drug production in bacteria
Vol.92：Numerical modelling to assist the development of a retinal prosthesis
Vol.93：Repurposing cancer drugs: An innovative therapeutic strategy to fight bone cancer
Vol.94：A berry vine found in Asia proves useful in combating lung cancer
Vol.95：A new avenue for detecting cancer in the blood
Vol.96：Automated cell image analysis
Vol.97：Artificial intelligence helps to determine cancer invasion
Vol.98：Okayama University launches clinical trials of a jawbone regeneration therapy using human BMP-2 transgenic protein derived from Escherichia coli.
Vol.99：A rapid flow process that can convert droplets into multilayer polymeric microcapsules
Vol.100：Understanding insect leg regeneration
Vol.101：Oral tumor progression mechanism identified
Vol.102：Controlled cell death by irradiation with light
Vol.103：High-quality growth
Vol.104：The determinants of persistent and severe COVID-19 revealed
Vol.105：The dynamics of skin regeneration revealed
Vol.106：The skin electrically modelled
Vol.107：COVID-19 mRNA vaccines and fever: A possible new link