Donor-Derived Multiple Leukemia Antigen-Specific T-cell Therapy to Prevent Relapse After Transplant in Patients With ALL

Authors

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
LaQuisa Hill
Robert A Krance
Caridad Martinez
Priti Tewari
Bilal Omer
Stephen Gottschalk
Helen E Heslop
Malcom K Brenner
Cliona M Rooney
Juan F Vera
Ann M Leen
Premal D Lulla

Language

English

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

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.

Keywords

Adult, Child, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Recurrence, Transplantation, Homologous

Published Open-Access

yes

Recommended Citation

Naik, Swati; Vasileiou, Spyridoula; Tzannou, Ifigeneia; et al., "Donor-Derived Multiple Leukemia Antigen-Specific T-cell Therapy to Prevent Relapse After Transplant in Patients With ALL" (2022). Faculty and Staff Publications. 1601.
https://digitalcommons.library.tmc.edu/baylor_docs/1601