Publication highlights May 2025

In this month’s blog, we highlight some recent publications citing the use of Olink’s PEA technology to analyze samples obtained during clinical trials. The rapidly increasing use of proteomic analysis as part of clinical trials is providing important data to maximize actionable insights from this critical and highly expensive phase of the drug development process. Such analyses can help to better stratify future trials, identify novel biomarkers to predict treatment outcomes and provide a deeper understanding of the mode of drug action.

Serum biomarkers of CAR T-cell expansion

The degree of expansion of the infused cell constructs is a key parameter in CAR T-cell therapy. Under-expansion can significantly reduce efficacy, while excessive expansion could lead to cytokine release syndrome (CRS) or other severe side effects. In a clinical trial for the use of anti-CD22 CAR T-cell therapy  in patients with B-cell acute lymphoblastic leukemia (B-ALL) who had relapsed after previous anti-CD19 CAR T-cell therapy, Olink® Explore 1536 was used to monitor serum protein responses.

This showed a highly significant correlation between CAR T-cell expansion and the protein ST1. This is an entirely novel finding, and interestingly SIT1 has been associated with negative regulation of the T-cell receptor based on in vitro studies. In addition, clear trends were also observed for the associations of TNF, IL-10, IL-6, IFNG, and CXCL9 with the degree of CRS in patients receiving the therapy.

Serum biomarkers predict disease recurrence after breast cancer therapy

The Olink Target 96 Immuno-oncology panel was used to measure serum proteomics as a primary outcome for samples taken from the OXEL clinical trial to compare chemotherapy (CT), immunotherapy (IT) and combined chemoimmunotherapy (CIT) in patients with triple-negative breast cancer showing residual disease.

The analysis showed that distinct sets of proteins associated with disease recurrence in response to the three treatment arms used. Multivariate analysis derived high-accuracy 2-protein  and 3-protein models that discriminated patients who would or would not show disease recurrence following  immunotherapy and chemotherapy respectively (AUCs > 0.9 in both cases).  Several of the proteins associated with disease recurrence also showed prognostic value in relation to the duration of invasive disease-free survival (iDFS).

Biomarkers of response to immunotherapy and antiangiogenics in endometrial cancer

In a phase II clinical trial to monitor the immune signatures of recurrent endometrial cancer patients treated with antiangiogenics combined with  immune checkpoint blockade (ICB) immunotherapy, the Olink Target 96 Immuno-oncology panel  was used as part of a multiomic examination to compare mono- and combinational therapy responses.

The Olink analysis identified 3 groups of markers that were specifically upregulated after combination therapy, downregulated only in response to  combination therapy, or increased after both mono- or combinational immunotherapy. In addition to these insights into the effects of the therapeutic options, baseline levels of some proteins were also shown to correlate with poor overall and progression-free survival, and to severe adverse events.

The molecular basis of response to oncolytic virotherapy in melanoma patients

In  a phase 1 clinical trial for use of the OH2 oncolytic virus in patients who previously received standard immunotherapy for advanced melanoma, the Olink Target 96 Inflammation panel was used to compare longitudinal proteomics between patients who did or didn’t show clinical benefit from the treatment.

Nine proteins measured at baseline were all significantly higher in patients receiving no clinical benefit from OH2, while at the 12-month timepoint, a total of 21 markers were differentially expressed between the groups. Enrichment analysis highlighted neutrophil chemotaxis as a key process linked to poorer outcome, which could be corroborated by observations that peripheral blood neutrophil levels were significantly higher in patients showing no benefit from OH2 therapy.