Lexington, Mass.– Agenus Inc. has presented new findings at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting that suggest its experimental therapy botensilimab may significantly improve immune response in a common, treatment-resistant form of colorectal cancer. The company’s study shows that botensilimab “switches on” the immune system’s T cells to recognize and attack microsatellite stable (MSS), or mismatch repair proficient (pMMR), metastatic colorectal cancer—a form that makes up 85–95% of all colorectal cancer cases and has historically been unresponsive to immunotherapy.
The research, led by Dr. Gertjan Rasschaert of Leuven University Hospitals in collaboration with Agenus, KU Leuven, and immune-profiling company Omniscope, highlights botensilimab’s potential to convert immunologically “cold” tumors into “hot” ones, meaning they become recognizable and targetable by the immune system.
According to Agenus Vice President of Research Dr. Dhan Chand, Ph.D., the data offer strong evidence of botensilimab’s ability to enhance T-cell priming, activation, and diversity—critical steps in generating a potent immune response. The study revealed that T cells begin activating within two weeks of treatment, sustain activity throughout the therapy cycle, and expand in number. Immune system changes were often detectable through blood tests even before traditional imaging picked up signs of tumor response.
These findings suggest that immune biomarkers could help identify which patients are most likely to benefit from botensilimab, enabling earlier and more precise treatment decisions. “Our findings offer new insight into how patients with immunotherapy-resistant colorectal cancer are responding at the immune level,” said Chand. “This could be a meaningful step forward for a population of patients with limited therapeutic options.”
Dr. Steven O’Day, Chief Medical Officer at Agenus, said the data mark a potentially significant advance for patients facing one of the most challenging types of colorectal cancer. “Botensilimab is showing real promise in overcoming resistance by activating the body’s own T cells and making these tumors visible to the immune system,” he said.
The presentation adds momentum to ongoing efforts to expand the role of immunotherapy in solid tumors that have traditionally resisted treatment. Botensilimab remains in clinical development, with further studies underway to validate its efficacy and expand its use across multiple cancer types.
