This talk will discuss the evolving landscape of biomarkers in the field of immuno-oncology, on immunohistochemistry and genomic approaches, for both immune-checkpoint single-agent treatments and combination therapies.

We will share advancements in multi-biomarker CTC analysis and introduce the Orion spatial biology platform for multiplex tissue analysis.  Orion’s single day workflow for 21-channel whole-slide imaging enables immuno-oncology and infectious disease applications.  In addition, multi-biomarker CTC assays with high accuracy and precision suitable for multi-center trials will be reviewed.

Gritstone Oncology is a cancer immunotherapy company working to help patients with the most difficult-to-treat tumors. Gritstone’s personalized immunotherapy process leverages our EDGE AI platform to predict neoantigens that will be presented on a patient’s tumor, allowing us to create a patient-specific heterologous prime boost immunotherapy that is designed to elicit a potent anti-tumor T cell response.

The progress of immunotherapy has been remarkable for patients with lung cancer. While we have focused on a “single” biomarker assay for immunotherapy, it might be time to look into the role of “combined” biomarkers or assays for the most optimal selection of patients who benefit from immunotherapy. The current role of PD-L1 and TMB as predictive biomarkers will be discussed as well as potential new biomarkers for immunotherapy, such as genomic classifiers and the role of the microbiome for immunotherapy of lung cancer.

Over the last decades, several assays that detect immunophenotypic or genetic/molecular abnormalities of AML cells have been developed to quantify MRD in AML. While methodologies continue to evolve, existing data indicate MRD test results are useful for the refinement of prognosis/risk stratification. There is increasing interest in using information from MRD tests for therapeutic decision-making, as well as a surrogate endpoint for drug testing/approval, but well-controlled data supporting these uses are currently lacking.

For many diseases, population screening is essential to improving patient survival. Despite the promise of blood-based “liquid biopsies," progress has been limited necessitating new multi-omics approaches incorporating multiple technologies. We discuss new approaches to biomarker discovery, algorithm development, and clinical validation using mechanistic, statistical, and machine learning approaches for handling of multi-omics data. We further discuss the need to improve clinical decision support systems to facilitate clinical decision making.

GRAIL is a healthcare company whose mission is to detect cancer early, when it can be cured. GRAIL is focused on alleviating the global burden of cancer by developing pioneering technology to detect and identify multiple deadly cancer types early. The company is using the power of next-generation sequencing, population-scale clinical studies, and state-of-the-art computer science and data science to enhance the scientific understanding of cancer biology, and to develop its multi-cancer early detection blood test.

Blood is accessible with minimally invasive and cost-effective methods, so it has always been considered an attractive source of biomarkers. With rapid technological advancements, circulating tumor DNA (ctDNA), in particular, has become an invaluable diagnostic material with multiple potential applications across the disease continuum. Here, we review the recent findings on ctDNA to aid in patient selection and disease monitoring from an immuno-oncology perspective, and we discuss potential future directions.

Next-generation IHC platforms analyze around thirty-nine markers at a time followed by a two-dimensional multilayer-image translation of the atomic mass numbers registered by pixel, from a tissue section surface previously incubated with a cocktail of isotope-conjugated antibodies; revealing the multi-epitope composition of malignant cells and tumor-infiltrating immune cells. By these platforms, the immune contexture of tumors can be revealed to correlate clinical outcomes, tumor-specific biomarkers, and the quality of immune response. An immuno-oncology panel for immune-profiling or malignant tumor tissues was optimized for IMC and MIBI imaging systems.

Saliva is a bodily fluid that we produce ~600ml per day and harbors multiple omics constituents that can be harnessed non-invasively and painlessly for personalized and precision medicine, making it ideal for liquid biopsy applications. Yet, PCR-based technologies cannot detect ctDNA in saliva samples, whereas an emerging liquid biopsy platform “Electric Field Induced Release and Measurement (EFIRM)” can consistently detect ctDNA from NSCLC patients with actionable mutations in plasma and saliva with concordance of 95%+ with tissue/biopsy-based genotyping, including early stage lesions.

Early detection of cancer has the potential to significantly reduce cancer deaths. Liquid biopsies provide an opportunity to develop tests for the detection of multiple-types of cancer in a single test. We will discuss the opportunities and the challenges of developing and utilizing such test.

Exosomes reflect promising cancer biomarkers due to their abundance in biofluids, protein, and RNA contents reflecting parental cells, and stability in circulation. Pancreatic ductal adenocarcinomas (PDAC) represent highly lethal cancers often presenting at advanced stages. Integrating exosomes into monitoring programs for PDAC could improve clinical outcomes. This talk will discuss novel nanosensors we developed to analyze exosomes in blood and recent translational strategies to position them into clinical workflows.