Donor-derived multiple leukemia antigen–specific T-cell therapy to prevent relapse after transplant in patients with ALL

Swati Naik, Spyridoula Vasileiou, Ifigeneia Tzannou, Manik Kuvalekar, Ayumi Watanabe, Catherine Robertson, Natalia Lapteva, Wang Tao, Mengfen Wu, Bambi Grilley, George Carrum, Rammurti T. Kamble, La Quisa Hill, Robert A. Krance, Caridad Martinez, Priti Tewari, Bilal Omer, Stephen Gottschalk, Helen E. Heslop, Malcom K. BrennerCliona M. Rooney, Juan F. Vera, Ann M. Leen, Premal D. Lulla

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2706-2711
Number of pages6
JournalBlood
Volume139
Issue number17
DOIs
StatePublished - Apr 28 2022

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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