Haploidentical stem cell transplantation is increasingly used worldwide as an alternative donor transplantation method. Although novel preparative regimens and T-cell deletion techniques have improved engraftment rates and viral safety, relapses of the underlying leukemia/lymphoma are still frequent, thus representing a significant and unsolved problem. Recent technological advances now enable us to individually decipher the MHC-associated immunopeptidome of cancer cells in reasonable time. These tumor-specific peptides can then be used to skew the early immune reconstitution toward anti-leukemia T-cell responses. In this meeting contribution, we summarize recent innovations in the field and present preliminary data on using this technique for cancer epitope discovery in a paradigmatic pediatric brain tumor with very low mutational burden.