An Interview with Dr. Henning Zelba
In a retrospective observation of 52 patients with IDH1-mutant gliomas, a form of brain tumor, researchers investigated whether individualized peptide therapies can trigger targeted immune responses. IDH1-mutant gliomas typically have a low mutational burden, which limits the number of neoantigens and makes them challenging targets for immunotherapy. Each therapy was individually designed based on the patient’s tumor profile and contained at least one peptide targeting the shared IDH1 mutation. The results demonstrated that even in tumors with few mutations, carefully selected neoantigen targets can induce robust T-cell responses. Dr. Henning Zelba, the first author of the publication, discusses what these findings reveal about tumor-immune interactions and how diagnostic precision could help advance future immunotherapeutic strategies. In the interview, he also highlights the contribution of CeGaT’s NGS services portfolio to the publication.
What insights did your immune monitoring approach provide in the course of this work?
“Our aim was to characterize the T-cell responses induced by an individualized, neoantigen-derived peptide-based therapy. Specifically, we analyzed the phenotype of neoantigen-specific T-cells and their cytokine profiles. We confirmed that the therapy elicits strong immune responses, as previously shown in glioblastoma patients. These findings reinforce the high immunogenic potential of the peptide-based therapy.“
What technologies or assays did you use to characterize immune responses?
“In addition to classical immunological wet lab methods, we used CeGaT’s T-Cell Receptor Sequencing product to generate a candidate list of TCRβ CDR3 sequences targeting mutIDH1. These sequences were then tracked in samples processed with CeGaT’s Single-Cell Immune Profiling product. This enabled us to reconstruct the full-length alpha and beta chains and analyze the transcriptomic profiles of neoantigen-specific T-cells at single-cell resolution. The combination of both technologies allows a detailed functional and molecular characterization, although it requires high-quality, well-preserved samples and a robust data pipeline.“
What role did T-cell receptor (TCR) analysis play in understanding patient responses?
“We used the TCRβ CDR3 sequence of neoantigen-specific T-cells as a molecular barcode. This allowed us to track these T-cells in blood and tumor tissue before and after treatment. It provided us with valuable insights into how peptide-based therapy shapes the persistence and distribution of T-cell responses.“
How could immune monitoring be further refined to predict clinical benefit more accurately?
”We observed a correlation between the amount of T-cell responses induced by peptide-based therapy and patient survival: individuals with a high number of induced T-cell responses lived longer than those with few or absent responses. This suggests that immune monitoring could serve as an early indicator of clinical benefit and supports further development of immunogenicity-based biomarkers.“
For full details, see the original publication: