Gwangju Institute of Science and Technology (GIST) and Genome & Company have jointly discovered a new immuno-oncology target, CNTN4, and developed a corresponding inhibitory antibody, GENA-104. This breakthrough offers potential for treating patients who do not respond to existing immuno-oncology therapies.
The research, led by Professor Park Han-soo from GIST and the Genome & Company team, elucidated the role of CNTN4 in suppressing T cell proliferation and cytokine secretion. CNTN4 was found to inhibit T cell receptor signaling and transcription factor movement into the nucleus, effectively dampening the immune response against cancer cells. Notably, CNTN4 is overexpressed in various carcinomas, including gastric, liver, and pancreatic cancers.
GENA-104: A Novel CNTN4 Inhibitory Antibody
To counteract the inhibitory effects of CNTN4, the research team developed GENA-104, an antibody designed to specifically bind to and inhibit CNTN4. In vitro studies demonstrated that GENA-104 effectively restored T cell proliferation and cytokine secretion that had been suppressed by CNTN4. Animal studies further validated these findings, showing a significant reduction in tumor size upon administration of GENA-104, with tumor growth inhibition rates reaching approximately 75%.
"GENA-104 effectively offsets CNTN4-induced T-cell inhibitory action and has strong therapeutic potential in tumor models," the research team stated.
Clinical Implications and Future Directions
Analysis of existing clinical data revealed that patients who responded positively to current immuno-oncology drugs exhibited high levels of CNTN4. Conversely, higher CNTN4 expression correlated with lower survival rates and poorer prognoses. This inverse relationship suggests that GENA-104 could be particularly beneficial for patients who have not responded to conventional immuno-oncology treatments.
"This means that GENA-104, a CNTN4 inhibitory antibody, is highly likely to be effective for patients who have not responded to existing immuno-oncology drugs," the researchers explained.
The findings were published online in Science Immunity. Professor Park emphasized the academic significance of the study, stating that it demonstrates the potential for GENA-104 to succeed as a novel cancer immunotherapy.
Genome & Company continues to innovate in the antibody-drug conjugate (ADC) field, having previously licensed out its GENA-111 antibody technology to DivioPharm in a deal valued at 586 billion won.
