Although hematopoietic stem cell transplantation (HSCT) is a curative option for individuals with high-risk acute lymphoblastic leukemia (ALL), recurrence is still a primary cause of therapy failure. To prevent disease recurrence, researchers produced and infused donor-derived multiple leukemia antigen-specific T cells (mLSTs) targeting the leukemia-associated antigens PRAME, WT1, and survivin, which are often expressed in B- and T-ALL. Their objective was to increase the effect of graft-versus leukemia while limiting the danger of graft-versus-host illness (GVHD).
They gave mLSTs (dose range, 0.5 × 107 to 2 × 107 cells per square meter) to 11 ALL patients (8 pediatric, 3 adults), and there was no dose-limiting toxicity, acute GVHD, or cytokine release syndrome. Six of the eight evaluable patients were still in long-term full remission (median: 46.5 months; range, 9-51).
They found a rise in the frequency of tumor-reactive T-cells in the patients immediately after infusion, with activity against both targeted and nontargeted, recognized tumor-associated antigens, indicating in vivo antigen transmission. The in vivo amplification, on the other hand, was not present in the two individuals who relapsed. In conclusion, infusion of donor-derived mLSTs following allogeneic HSCT is possible and safe, and it may help in disease management, as indicated by tumor-directed T-cell proliferation in vivo. As a result, the technique provided a viable option for avoiding recurrence in ALL patients.
