Abstract:
:Immunotherapy is the revolution in cancer treatment of this last decade. Among multiple approaches able to harness the power of the immune system against cancer, T cell based immunotherapies represent one of the most successful examples. In particular, biotechnological engineering of protein structures, like the T cell receptor or the immunoglobulins, allowed the generation of synthetic peptides like chimeric antigen receptors and bispecific antibodies that are able to redirect non-tumor specific T cells to recognize and kill leukemic cells. The anti-CD19/CD3 bispecific antibody blinatumomab and anti-CD19 chimeric antigen receptor T cells (CART19) have produced deep responses in patients with relapsed and refractory B-cell acute leukemias. However, although the majority of these patients responds to anti-CD19 immunotherapy, a subset of them still relapses. Interestingly, a novel family of leukemia escape mechanisms has been described, all characterized by the apparent loss of CD19 on the surface of leukemic blasts. This extraordinary finding demonstrates the potent selective pressure of CART19/blinatumomab that drives extreme and specific escape strategies by leukemic blasts. Patients with CD19-negative relapsed leukemia have very poor prognosis and novel approaches to treat and ideally prevent antigen-loss are direly needed. In this review we discuss the incidence, mechanisms and therapeutic approaches for CD19-negative leukemia relapses occuring after CD19-directed T cell immunotherapies and present our future perspective.
journal_name
Comput Struct Biotechnol Jjournal_title
Computational and structural biotechnology journalauthors
Ruella M,Maus MVdoi
10.1016/j.csbj.2016.09.003subject
Has Abstractpub_date
2016-09-28 00:00:00pages
357-362issn
2001-0370pii
S2001-0370(16)30062-9journal_volume
14pub_type
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
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pub_type: 杂志文章,评审
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更新日期:2018-08-17 00:00:00
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journal_title:Computational and structural biotechnology journal
pub_type: 杂志文章,评审
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journal_title:Computational and structural biotechnology journal
pub_type: 杂志文章,评审
doi:10.1016/j.csbj.2017.01.007
更新日期:2017-01-19 00:00:00
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
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doi:10.1016/j.csbj.2019.12.001
更新日期:2019-12-17 00:00:00
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
pub_type: 杂志文章,评审
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
pub_type: 杂志文章,评审
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journal_title:Computational and structural biotechnology journal
pub_type: 杂志文章
doi:10.1016/j.csbj.2020.04.006
更新日期:2020-04-09 00:00:00
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journal_title:Computational and structural biotechnology journal
pub_type: 杂志文章,评审
doi:10.1016/j.csbj.2020.12.031
更新日期:2020-12-27 00:00:00
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journal_title:Computational and structural biotechnology journal
pub_type: 杂志文章,评审
doi:10.1016/j.csbj.2020.06.010
更新日期:2020-06-13 00:00:00
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
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journal_title:Computational and structural biotechnology journal
pub_type: 杂志文章,评审
doi:10.1016/j.csbj.2020.11.007
更新日期:2020-11-14 00:00:00