We have entered a new era of modern science, where therapeutic innovation is reshaping the field of medicine. From immuno-oncology to neurodegeneration, the therapies reaching patients today are more complex, more costly, and more ambitious in their biological scope than ever before. The emergence of advanced modalities, CAR T cells, engineered bispecific antibodies, RNA-based therapies, and oncolytic platforms has fundamentally changed what is required of biomarker science. Unlike small molecules or traditional biologics, these therapies act through multi-layered mechanisms: cell trafficking, dynamic cytokine signalling, immune synapse formation, and tissue microenvironment remodelling. Their therapeutic success and their risks hinge on networks rather than single targets.
To support the development of next-generation therapies, we need biomarker approaches that are capable of revealing systems-level biology. At Synexa, our focus has been on generating mechanistic insights that help customers make more informed translational decisions. Choosing the right multiplex platform requires balancing sensitivity, reproducibility, and scalability with the practical needs of translational science. Among the many options available (mass spectrometry, Luminex, MSD, Somascan) we selected Olink’s proximity extension assay (PEA) as a cornerstone of our biomarker programs. The decision was guided by both technical and practical considerations:
Technical Rationale
- High specificity and sensitivity: Dual antibody binding with DNA-based extension minimises cross-reactivity and allows detection of low-abundance proteins in complex matrices such as cerebrospinal fluid, synovial fluid, or bronchoalveolar lavage.
- Minimal sample requirement: Olink panels require as little as 1-3 µL of plasma or serum, making them ideal for rare matrices and longitudinal studies where sample volume is limiting.
- Reproducibility and standardisation: Built-in internal controls and inter-plate normalisation ensure that data can be compared across time points, batches, and even across studies.
Practical Advantages
- Biology-driven panel design: Themed panels (immunology, neurology, cardiometabolic, oncology, inflammation) provide coverage of well-annotated biological pathways, enabling direct mechanistic interpretation.
- Breadth with specificity: Measuring hundreds to thousands of proteins simultaneously, from canonical cytokines to less obvious regulators of metabolism and tissue repair.
- Scalability from targeted to exploratory: From 48 and 96-protein panels to broad Olink Reveal, we can move flexibly between hypothesis-driven and discovery-driven studies without changing underlying technology.
Olink in Action: Addressing Complexity and Heterogeneity
The value of Olink becomes clearest in clinical settings where biology is complex and patient responses are heterogeneous. Several recent trials demonstrate how multiplex proteomics can reveal insights that single-plex assays would otherwise miss.
- In cell therapy trials, Olink Explore was applied to monitor patients receiving anti-CD22 CAR T therapy after relapse on CD19-directed CAR T cells. In addition to the well-established cytokine surges of IL-6, TNF, and IFN-γ linked to cytokine release syndrome, multiplex profiling uncovered unexpected signals such as SIT1, which strongly correlated with CAR T expansion and treatment response (J Immunother Cancer, 2025). This type of emergent signal is difficult to capture with targeted single-plex assays.
- In immuno-oncology, a re-analysis of the Lung-MAP S1400I phase III trial (immune checkpoint therapy in squamous NSCLC) used Olink Target 96 to profile baseline proteomic signatures. Patients with immune-activation signatures had better responses, whereas those with stromal or hyper-inflammatory signals fared worse. Importantly, these proteomic stratifiers were independent of genomic and transcriptomic predictors, highlighting the complementarity of proteomics in complex patient cohorts (Clin Cancer Res, 2024).
- Even in solid tumours with limited therapeutic options, such as pancreatic cancer, Olink was used to derive a seven-protein signature to predict early disease progression before the start of treatment (or early on-treatment) predictive of progression in patients on FOLFIRINOX chemotherapy. Elevated pre-treatment plasma levels of VEGFA, ITGB6, PRDX3, MYO9B, SIT1, and BACH1 and low pre-treatment plasma levels of GAL were significantly associated with PDAC progression after four cycles of FOLFIRINOX. These associations remained significant after one FOLFIRINOX cycle for PRDX3, MYO9B, SIT1, and BACH1. Most interestingly, elevated VEGFA and PRDX3 pre-treatment levels correlated with poor treatment response (Euro J of Cancer, 2024).
Together, these examples highlight a consistent theme: when biology is multi-layered and patient heterogeneity is high, multiplex proteomics reveals patterns that reshape how we interpret trial outcomes.
From Data to Decisions: How We Integrate Olink
For our customers, the ultimate value of multiplex proteomics lies not only in the data but in how it is interpreted and integrated with other biological readouts. At Synexa, we utilise Olink as one layer within a multi-omics framework that combines cellular, molecular, spatial, and clinical information to generate actionable insights.
- Flow cytometry provides the cellular context, tracking the expansion, activation, and persistence of immune populations in blood and tissue.
- Transcriptomics complements proteomics by identifying gene-level changes, while Olink captures the functional protein-level outputs of these pathways.
- Imaging and histology add spatial resolution, revealing where therapeutic and immune cells interact within the tissue microenvironment.
- Clinical metadata such as patient demographics, disease stage, prior treatments, comorbidities, and clinical outcomes provide the essential backdrop for interpretation, ensuring that signatures are clinically meaningful.
By bringing these layers together, we move beyond descriptive biomarker lists toward mechanistic models of disease and therapy. This integrative approach provides a systems-level view that strengthens decision-making at every stage of development:
- Early-phase trials: identifying predictive markers of response and toxicity.
- Pivotal studies: stratifying heterogeneous patient populations.
- Post-marketing: monitoring long-term safety and efficacy.
Conclusion
As drug development advances into increasingly complex modalities, the need for systems-level biomarkers has never been greater. Disease outcomes are shaped by networks of interacting cells and proteins, not by single markers in isolation. Olink’s multiplex proteomics platform enables us to capture this complexity with sensitivity, reproducibility, and clinical relevance, thereby transforming data into mechanistic insights.
At Synexa, we see Olink not as a stand-alone assay but as a cornerstone of an integrated biomarker strategy, aligned with flow cytometry, transcriptomics, and imaging to build a coherent view of therapeutic biology. This approach enables our customers to navigate patient heterogeneity, anticipate risks, and identify the mechanisms that drive efficacy and resistance.
