Why functional immune readouts matter
Published: August 22, 2025
3 minute read
Authored by: Jens Gertow
Translating promising cancer vaccines into effective clinical tools hinges on accurately measuring the functional immune response they induce. Among immunoassays, ELISpot has become a gold standard for monitoring cellular immunity, valued for its sensitivity, quantitative power, and adaptability.
Why ELISpot remains indispensable in immune monitoring
ELISpot brings several key advantages in the context of early-phase immunotherapy trials.
- Single cell functional resolution: Each cytokine-secreting cell generates a spot, so you can directly quantify frequency and function, instead of inferring activity from bulk measures.
- High sensitivity: Capable of detecting as few as 25 IFN-γ–producing cells per million PBMCs.
- Cost effective and standardizable: Requires modest instrumentation and is well-suited for multi site clinical trials and resource-limited settings. And proficiency panels, ELISpot can achieve inter-laboratory CVs under 20%, making it reliable for clinical-grade biomarker use.
How ELISpot illuminated immune engagement in the MVX-ONCO-1 trial
The first-in-human Phase I study of MVX-ONCO-1, a personalized cancer vaccine combining irradiated autologous tumor cells and sustained GM CSF delivery via encapsulated cells, demonstrated clinical promise in advanced solid tumors (>50 % clinical benefit; one patient achieving 7 years disease free survival).
To assess immune engagement, researchers deployed IFN-γ ELISpot, stimulating PBMCs with autologous tumor cells or tumor-associated antigen. Among patients surviving beyond 6 months, 50 % showed increased IFN-γ ELISpot responses compared to baseline. In contrast, none of the patients with survival under 6 months mounted ELISpot-detectable responses. In addition, in chordoma patients, ELISpot against Brachyury (a tumor-specific marker) indicated immune specificity.
These findings suggest that ELISpot-detectable T-cell responses correlated with extended survival, positioning ELISpot as a valuable early functional biomarker in vaccine trials.
Why ELISpot adds value in early immunotherapy trials
1. Functional biomarker for treatment response: By linking IFN-γ secreting T cells to clinical survival outcomes, ELISpot provides actionable evidence of vaccine efficacy.
2. Sensitive detection of emerging or subclinical responses: Detects low-frequency, vaccine-induced T-cell activation that could be missed by other assays.
3. Supports broad cancer vaccine strategies: The flexibility to test patient-specific antigens (e.g., autologous tumor cells, Brachyury) showcases ELISpot's adaptability in personalized immunotherapy.
4. Practical for clinical and multi-center use: ELISpot’s scalability and standardization make it ideal for early-phase trials seeking reproducible immune metrics.
Concluding perspective
The MVX-ONCO-1 trial highlights how an innovative, personalized cancer immunotherapy can be evaluated not just for safety, but for functional immunogenicity – and there, ELISpot excels. Its sensitivity, practicality, and correlation with clinical outcomes reinforce its role as an essential tool in the immunotherapy biomarker toolbox. Incorporating ELISpot enables researchers to link vaccine-induced immune activation to patient benefit, guiding both development and personalized application.
References
Vernet et al., A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors, Cancer Research Communications 2024
Mabtech products used in this study