Posttransplant chimeric antigen receptor therapy Journal Article

Authors: Smith, M.; Zakrzewski, J.; James, S.; Sadelain, M.
Article Title: Posttransplant chimeric antigen receptor therapy
Abstract: Therapeutic T-cell engineering is emerging as a powerful approach to treat refractory hematological malignancies. Its most successful embodiment to date is based on the use of second-generation chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule found in most B-cell leukemias and lymphomas. Remarkable complete remissions have been obtained with autologous T cells expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic hematopoietic stem cell transplantation. However, the use of donor T cells poses unique challenges owing to potential alloreactivity. We review different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor–deficient T cells, lymphoid progenitor cells, and regulatory T cells. Advances in CAR design, T-cell selection and gene editing are poised to enable the safe use of allogeneic CAR T cells without incurring GVHD. © 2018 by The American Society of Hematology.
Keywords: review; nonhuman; t lymphocyte receptor; regulatory t lymphocyte; hematologic malignancy; pre t lymphocyte; graft versus host reaction; chimeric antigen receptor; donor lymphocyte infusion; allogeneic hematopoietic stem cell transplantation; t cell depletion; lymphoid progenitor cell; cd19 antigen; alloimmunity; clinical outcome; cell engineering; human; priority journal; gene editing; chimeric antigen receptor t-cell immunotherapy
Journal Title: Blood
Volume: 131
Issue: 10
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2018-03-08
Start Page: 1045
End Page: 1052
Language: English
DOI: 10.1182/blood-2017-08-752121
PROVIDER: scopus
PMCID: PMC5865610
PUBMED: 29358181
Notes: Review -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. Michel W J Sadelain
    449 Sadelain
  2. Melody Smith
    13 Smith
  3. Scott E James
    3 James