T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Chapuis, Aude GEgan, Daniel N
Bar, Merav
Schmitt, Thomas M
McAfee, Megan S
Paulson, Kelly G
Voillet, Valentin
Gottardo, Raphael
Ragnarsson, Gunnar B
Bleakley, Marie
Yeung, Cecilia C
Muhlhauser, Petri
Nguyen, Hieu N
Kropp, Lara A
Castelli, Luca
Wagener, Felecia
Hunter, Daniel
Lindberg, Marcus
Cohen, Kristen
Seese, Aaron
McElrath, M Juliana
Duerkopp, Natalie
Gooley, Ted A
Greenberg, Philip D
Issue Date
2019-07
Metadata
Show full item recordCitation
T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. 2019, 25(7):1064-1072 Nat MedAbstract
Relapse after allogeneic hematopoietic cell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) entering HCT with poor-risk features1-3. When HCT does produce prolonged relapse-free survival, it commonly reflects graft-versus-leukemia effects mediated by donor T cells reactive with antigens on leukemic cells4. As graft T cells have not been selected for leukemia specificity and frequently recognize proteins expressed by many normal host tissues, graft-versus-leukemia effects are often accompanied by morbidity and mortality from graft-versus-host disease5. Thus, AML relapse risk might be more effectively reduced with T cells expressing receptors (TCRs) that target selected AML antigens6. We therefore isolated a high-affinity Wilms' Tumor Antigen 1-specific TCR (TCRC4) from HLA-A2+ normal donor repertoires, inserted TCRC4 into Epstein-Bar virus-specific donor CD8+ T cells (TTCR-C4) to minimize graft-versus-host disease risk and enhance transferred T cell survival7,8, and infused these cells prophylactically post-HCT into 12 patients ( NCT01640301 ). Relapse-free survival was 100% at a median of 44 months following infusion, while a concurrent comparative group of 88 patients with similar risk AML had 54% relapse-free survival (P = 0.002). TTCR-C4 maintained TCRC4 expression, persisted long-term and were polyfunctional. This strategy appears promising for preventing AML recurrence in individuals at increased risk of post-HCT relapse.Description
To access publisher's full text version of this article click on the hyperlink belowAdditional Links
https://www.nature.com/articles/s41591-019-0472-9ae974a485f413a2113503eed53cd6c53
10.1038/s41591-019-0472-9
Scopus Count
Collections
Related articles
- Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia.
- Authors: Gyurkocza B, Gutman J, Nemecek ER, Bar M, Milano F, Ramakrishnan A, Scott B, Fang M, Wood B, Pagel JM, Baumgart J, Delaney C, Maziarz RT, Sandmaier BM, Estey EH, Appelbaum FR, Storer BE, Deeg HJ
- Issue date: 2014 Apr
- Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse.
- Authors: Shah NN, Loeb DM, Khuu H, Stroncek D, Ariyo T, Raffeld M, Delbrook C, Mackall CL, Wayne AS, Fry TJ
- Issue date: 2016 Dec
- Wilms' tumor gene 1 transcript levels in leukapheresis of peripheral blood hematopoietic cells predict relapse risk in patients autografted for acute myeloid leukemia.
- Authors: Messina C, Candoni A, Carrabba MG, Tresoldi C, Sala E, Tassara M, Crippa A, Peccatori J, Assanelli A, Gattillo S, Bellio L, Fanin R, Ciceri F, Bernardi M
- Issue date: 2014 Oct
- Cytomegalovirus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation is Associated with a Reduced Risk of Relapse in Patients with Acute Myeloid Leukemia Who Survived to Day 100 after Transplantation: The Japan Society for Hematopoietic Cell Transplantation Transplantation-related Complication Working Group.
- Authors: Takenaka K, Nishida T, Asano-Mori Y, Oshima K, Ohashi K, Mori T, Kanamori H, Miyamura K, Kato C, Kobayashi N, Uchida N, Nakamae H, Ichinohe T, Morishima Y, Suzuki R, Yamaguchi T, Fukuda T
- Issue date: 2015 Nov
- Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.
- Authors: Duncan CN, Majhail NS, Brazauskas R, Wang Z, Cahn JY, Frangoul HA, Hayashi RJ, Hsu JW, Kamble RT, Kasow KA, Khera N, Lazarus HM, Loren AW, Marks DI, Maziarz RT, Mehta P, Myers KC, Norkin M, Pidala JA, Porter DL, Reddy V, Saber W, Savani BN, Schouten HC, Steinberg A, Wall DA, Warwick AB, Wood WA, Yu LC, Jacobsohn DA, Sorror ML
- Issue date: 2015 Jan