Publication Date
4-28-2022
Journal
Blood
DOI
10.1182/blood.2021014648
PMID
35134127
PMCID
PMC9053698
PubMedCentral® Posted Date
4-28-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Adult, Child, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Recurrence, Transplantation, Homologous
Abstract
Hematopoietic stem cell transplant (HSCT) is a curative option for patients with high-risk acute lymphoblastic leukemia (ALL), but relapse remains a major cause of treatment failure. To prevent disease relapse, we prepared and infused donor-derived multiple leukemia antigen-specific T cells (mLSTs) targeting PRAME, WT1, and survivin, which are leukemia-associated antigens frequently expressed in B- and T-ALL. Our goal was to maximize the graft-versus-leukemia effect while minimizing the risk of graft-versus-host disease (GVHD). We administered mLSTs (dose range, 0.5 × 107 to 2 × 107 cells per square meter) to 11 patients with ALL (8 pediatric, 3 adult), and observed no dose-limiting toxicity, acute GVHD or cytokine release syndrome. Six of 8 evaluable patients remained in long-term complete remission (median: 46.5 months; range, 9-51). In these individuals we detected an increased frequency of tumor-reactive T cells shortly after infusion, with activity against both targeted and nontargeted, known tumor-associated antigens, indicative of in vivo antigen spreading. By contrast, this in vivo amplification was absent in the 2 patients who experienced relapse. In summary, infusion of donor-derived mLSTs after allogeneic HSCT is feasible and safe and may contribute to disease control, as evidenced by in vivo tumor-directed T-cell expansion. Thus, this approach represents a promising strategy for preventing relapse in patients with ALL.
Graphical Abstract
Included in
Hematology Commons, Hemic and Lymphatic Diseases Commons, Medical Sciences Commons, Neoplasms Commons, Oncology Commons
Comments
Associated Data