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- PMID: 24888271
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Article: Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity
Title | Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity |
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Authors | |
Issue Date | 2015 |
Citation | Leukemia, 2015, v. 29, n. 2, p. 387-395 How to Cite? |
Abstract | Chimeric antigen receptor (CAR)-redirected cellular therapy is an attractive modality for cancer treatment. We hypothesized that allogeneic CAR-engineered CD45RA-negative T cells can control cancer and infection without the risk of graft-versus-host disease (GVHD). We used CD19 + MLL-rearranged leukemia as prototype because it is an aggressive and generally drug-resistant malignancy. CD45RA - cells that were transduced with anti-CD19 CAR containing 4-1BB and CD3ζ signaling domains effectively lysed MLL-rearranged leukemia cell lines and primary blasts in vitro. In a disseminated leukemia mouse model, CAR + CD45RA - cells significantly reduced leukemia burdens and prolonged overall survival without GVHD. CAR + cells were sustainable in blood, and all the treated mice remained leukemia-free even after they were re-challenged with leukemia cells. Despite the transduction process, CD45RA - cells retained recall activity both in vitro and in vivo against human pathogens commonly found in cancer patients. In comparison with CD45RA + cells, CD45RA - cells showed less allogeneic activity in mixed leukocyte reactions and in mouse models. Thus, the use of CAR + CD45RA - cells can separate GVHD from graft-versus-malignancy effect and infection control. These cells should also be useful in nontransplant settings and may be administered as off-the-shelf third-party cells. |
Persistent Identifier | http://hdl.handle.net/10722/294474 |
ISSN | 2023 Impact Factor: 12.8 2023 SCImago Journal Rankings: 3.662 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Chan, W. K. | - |
dc.contributor.author | Suwannasaen, D. | - |
dc.contributor.author | Throm, R. E. | - |
dc.contributor.author | Li, Y. | - |
dc.contributor.author | Eldridge, P. W. | - |
dc.contributor.author | Houston, J. | - |
dc.contributor.author | Gray, J. T. | - |
dc.contributor.author | Pui, C. H. | - |
dc.contributor.author | Leung, W. | - |
dc.date.accessioned | 2020-12-03T08:22:49Z | - |
dc.date.available | 2020-12-03T08:22:49Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Leukemia, 2015, v. 29, n. 2, p. 387-395 | - |
dc.identifier.issn | 0887-6924 | - |
dc.identifier.uri | http://hdl.handle.net/10722/294474 | - |
dc.description.abstract | Chimeric antigen receptor (CAR)-redirected cellular therapy is an attractive modality for cancer treatment. We hypothesized that allogeneic CAR-engineered CD45RA-negative T cells can control cancer and infection without the risk of graft-versus-host disease (GVHD). We used CD19 + MLL-rearranged leukemia as prototype because it is an aggressive and generally drug-resistant malignancy. CD45RA - cells that were transduced with anti-CD19 CAR containing 4-1BB and CD3ζ signaling domains effectively lysed MLL-rearranged leukemia cell lines and primary blasts in vitro. In a disseminated leukemia mouse model, CAR + CD45RA - cells significantly reduced leukemia burdens and prolonged overall survival without GVHD. CAR + cells were sustainable in blood, and all the treated mice remained leukemia-free even after they were re-challenged with leukemia cells. Despite the transduction process, CD45RA - cells retained recall activity both in vitro and in vivo against human pathogens commonly found in cancer patients. In comparison with CD45RA + cells, CD45RA - cells showed less allogeneic activity in mixed leukocyte reactions and in mouse models. Thus, the use of CAR + CD45RA - cells can separate GVHD from graft-versus-malignancy effect and infection control. These cells should also be useful in nontransplant settings and may be administered as off-the-shelf third-party cells. | - |
dc.language | eng | - |
dc.relation.ispartof | Leukemia | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/leu.2014.174 | - |
dc.identifier.pmid | 24888271 | - |
dc.identifier.pmcid | PMC4275423 | - |
dc.identifier.scopus | eid_2-s2.0-84922578588 | - |
dc.identifier.volume | 29 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 387 | - |
dc.identifier.epage | 395 | - |
dc.identifier.eissn | 1476-5551 | - |
dc.identifier.isi | WOS:000349445000015 | - |
dc.identifier.issnl | 0887-6924 | - |