Gradalis, a clinical-stage biotech company, published a peer-reviewed article in Scientific Reports detailing their novel exome sequencing procedure and bioinformatics pipeline for identifying clonal cancer signals. This process focuses on clonal Tumor Mutation Burden (cTMB), clonal Neoantigens (cNEO), and Intratumoral Heterogeneity (ITH) to identify optimal targets for immunotherapy and predict patient response. The study validated this approach and demonstrated that the clonal signal is preserved in Gradalis’ investigational immunotherapy, Vigil.
This research is important because it offers a potentially more precise and effective way to target cancer with immunotherapy. By focusing on clonal signals present in all cancer cells, as opposed to subclonal signals present only in subsets, the immune system can mount a more comprehensive attack. This targeted approach could lead to more consistent and durable clinical responses across various cancer types, addressing a significant unmet need in oncology. Moreover, the ability to pre-select patients likely to benefit from immunotherapy could optimize clinical trial design and improve patient outcomes.
The exome sequencing process utilizes paired tumor and normal samples to generate high-coverage sequence data. This data is processed through a bioinformatics pipeline that identifies single nucleotide variants, insertions, deletions, and MHC-1 alleles, leading to the prediction of neoantigen peptides and clonality analysis. The final report quantifies cTMB, cNEO, and ITH levels, providing crucial information for treatment selection. Gradalis partnered with Frontage Laboratories to develop and validate this pipeline, ensuring its clinical applicability. The study also confirmed the stability of the clonal signal within their Vigil therapy, a personalized immunotherapy derived from the patient’s own tumor. Vigil is designed to enhance the immune response to a patient’s unique tumor signature.
This research represents a significant step forward in the development of personalized cancer immunotherapy. The identification and validation of clonal signals as robust therapeutic targets, combined with a reliable method for their detection, could significantly improve treatment strategies. This discovery could lead to the development of more effective immunotherapies and improved patient selection for existing treatments, potentially ushering in an era of more personalized and effective cancer care.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
