Analysis of neoantigen distribution, presentation and recognition by vaccine-induced specific T cells

Acute lymphoblastic leukemia is the most common childhood cancer, and relapse after initial treatment remains a major clinical challenge. The IVAC-AN project investigated whether personalized peptide vaccines can activate the immune system to specifically target leukemia cells and help prevent relapse. In vaccinated patients, antigen-specific T cells were isolated from blood, and their T cell receptors (TCRs) were identified and re-engineered using gene editing. These TCRs were reintroduced into T cells and functionally tested in the lab. Several of the engineered T cells recognized and attacked cancer cells presenting the vaccinated neoantigens — tumor-specific protein fragments that arise from mutations. The results show that vaccination can induce protective, antigen-specific T cell responses. The established methods lay the foundation for future therapies, such as adoptive T cell transfer with patient-tailored TCRs or improved personalized vaccination strategies.