Background
Various immunotherapeutic approaches have shown promising outcomes in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients who are refractory to conventional treatment or suffer from relapse. Whilst the use of synthetic immunotherapies has been well- established in pediatric cancer treatment, the amplification of natural immune responses against tumor antigens remains relatively unexplored and is typically less effective compared to adult tumors due to the reduced mutational burden observed in pediatric malignancies. This study focuses on investigating the presence of endogenous T-cells targeting predicted tumor associated antigens (TAA’s) and neoantigens within the peripheral blood of BCP-ALL patients, which could potentially be used as targets for immunotherapies.
Methods
Eight pediatric ALL patients treated in the Pediatric Hematology and Oncology unit at the CHUV (Centre hospitalier universitaire vaudois) in Lausanne were included in this study. Tumor-associated antigens (TAAs) and neoantigens were predicted individually for each patient. One patient’s bone marrow sample and every patient’s peripheral blood cells were stimulated with their predicted antigens. The lymphocytic response was quantified by the production of pro-inflammatory cytokine secretion (INF𝛾) measured by enzyme-linked immunosorbent spot (ELISpot). Additionally for one patient, an intracellular cytokine staining assay was conducted after a second round of in vitro stimulation on peripheral blood cells.
Results
Seven out of eight patients mounted an endogenous response against one or more of the predicted peptides. Over all patients, around 40% of the predicted TAA’s elicited an immunogenic response in the peripheral blood following remission. In addition, we identified one patient with a strong and polyclonal CD4+ T-cell response targeting a specific putative neoantigen.
Conclusions
These findings support the hypothesis that pediatric patients can elicit an endogenous T-cell response to BCP-ALL antigens, which persists in peripheral blood after remission. These results highlight the potential of harnessing this intrinsic T-cell response as a promising approach for the development of immunotherapies in pediatric BCP-ALL. Further investigations with larger patient cohorts and long-term follow-up are warranted to validate these observations and explore their clinical implications.