TY - JOUR
T1 - Donor-derived multiple leukemia antigen–specific T-cell therapy to prevent relapse after transplant in patients with ALL
AU - Naik, Swati
AU - Vasileiou, Spyridoula
AU - Tzannou, Ifigeneia
AU - Kuvalekar, Manik
AU - Watanabe, Ayumi
AU - Robertson, Catherine
AU - Lapteva, Natalia
AU - Tao, Wang
AU - Wu, Mengfen
AU - Grilley, Bambi
AU - Carrum, George
AU - Kamble, Rammurti T.
AU - Hill, La Quisa
AU - Krance, Robert A.
AU - Martinez, Caridad
AU - Tewari, Priti
AU - Omer, Bilal
AU - Gottschalk, Stephen
AU - Heslop, Helen E.
AU - Brenner, Malcom K.
AU - Rooney, Cliona M.
AU - Vera, Juan F.
AU - Leen, Ann M.
AU - Lulla, Premal D.
N1 - Funding Information:
This work was supported by the Leukemia and Lymphoma Society Specialized Center of Research (SCOR) awards 7001-14 (H.E.H.), a Cookies for Cancer Research grant (A.M.L.), Cancer Prevention and Research Institute of Texas (CPRIT) Texas Access to Cancer Cell Therapies (TACCT) grant RP180785, a CPRIT Early Career Clinical Investigator Award RP200584 (P.D.L.), an Edward P. Evans Foundation Discovery Research Grant (P.D.L.) 2018, and the Dan L. Duncan Comprehensive Cancer Center for application of the shared resources from a support grant from the National Institutes of Health (NIH), National Cancer Institute (P30CA125123). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2022 American Society of Hematology
PY - 2022/4/28
Y1 - 2022/4/28
N2 - 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.
AB - 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.
KW - Adult
KW - Child
KW - Graft vs Host Disease/etiology
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Humans
KW - Leukemia/therapy
KW - Recurrence
KW - Transplantation, Homologous/adverse effects
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UR - http://www.scopus.com/inward/citedby.url?scp=85129014722&partnerID=8YFLogxK
U2 - 10.1182/blood.2021014648
DO - 10.1182/blood.2021014648
M3 - Article
C2 - 35134127
AN - SCOPUS:85129014722
SN - 0006-4971
VL - 139
SP - 2706
EP - 2711
JO - Blood
JF - Blood
IS - 17
ER -