A collaborative research team from OSE Immunotherapeutics and Léon Bérard Cancer Center has developed a novel gene expression signature that could significantly improve prediction of patient responses to immunotherapy across multiple cancer types. The findings were presented at the American Association for Cancer Research (AACR) Annual Meeting held April 25-30, 2025, in Chicago.
The research addresses a critical challenge in cancer immunotherapy: while immune checkpoint blockade (ICB) therapies targeting PD-1, PD-L1, and CTLA-4 have revolutionized treatment for many cancers, current biomarkers used to predict patient responses have significant limitations.
New Biomarker Overcomes Current Limitations
Current predictive biomarkers like PD-L1 expression and tumor mutational burden (TMB) often produce inconsistent results. PD-L1 expression can vary significantly within tumors and between patients, making response prediction unreliable. This variability has driven the search for more universally applicable biomarkers.
The presentation, titled "A tumor agnostic composite gene expression signature identifies three groups of patients treated with immune checkpoint blockade with distinct clinical outcome," detailed the development and validation of a robust composite gene expression signature (cGES) that can predict both overall survival and progression-free survival in cancer patients receiving immune checkpoint inhibitors.
Professor Pierre Saintigny of Université Claude Bernard Lyon 1 and Centre Léon Bérard Comprehensive Cancer Center explained the significance: "Our collaborative research program validated a composite gene expression signature with a strong potential for stratifying and predicting clinical outcomes more accurately, which could significantly improve personalized treatment in clinical practice for ICB-treated patients, regardless of cancer type."
Clinical Applications and Patient Stratification
The new signature's tumor-agnostic nature represents a significant advancement over existing biomarkers. By identifying three distinct groups of patients with different clinical outcomes following immunotherapy, the signature could help clinicians make more informed treatment decisions.
Unlike previous RNA sequencing-based gene expression signatures that have had limited clinical adoption due to their specificity, this new approach aims to be broadly applicable across cancer types. This could potentially address the current gap between advanced genomic research and practical clinical implementation.
Broader Immuno-Oncology Innovations
The presentation was part of a broader showcase of OSE Immunotherapeutics' immuno-oncology portfolio at the AACR meeting. The company also presented updates on two other innovative platforms: OSE-CYTOMASK®, a CIS-Demasking cytokine bispecific technology, and CLEC-1, a novel immune checkpoint target.
OSE-CYTOMASK® employs a masking technology that keeps cytokines inactive until they reach specific immune cells like PD1-expressing T cells in the tumor microenvironment. This targeted approach aims to reduce systemic side effects while enhancing anti-tumor efficacy.
The CLEC-1 program focuses on a newly identified immune checkpoint expressed on myeloid and endothelial cells that can inhibit key anti-tumor immune functions. Preclinical studies have demonstrated that targeting CLEC-1 with specific antibodies could offer a promising new treatment approach, either as monotherapy or in combination with other agents.
Advancing Personalized Cancer Treatment
Aurore Morello, Head of Research and Director of R&D programs at OSE Immunotherapeutics, highlighted the company's commitment to innovation: "We are very happy to present the latest advancements from our ground-breaking preclinical programs, showcasing our unwavering commitment to innovative research."
The Centre Léon Bérard, a comprehensive cancer center in France, brings significant expertise to this collaboration. As a regional, national, and internationally recognized reference center, it focuses on integrated cancer management from diagnosis through treatment.
This research represents an important step toward more personalized cancer treatment, potentially allowing clinicians to better match patients with the immunotherapies most likely to benefit them, while sparing others from treatments unlikely to be effective.
