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Related Concept Videos

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Related Experiment Video

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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
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Immune-Based Therapies in Acute Leukemia.

Matthew T Witkowski1, Audrey Lasry1, William L Carroll2

  • 1Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.

Trends in Cancer
|November 11, 2019
PubMed
Summary

Treatment resistance in acute leukemia necessitates new strategies. This review explores how leukemia cells and their environment cause resistance to immune therapies like CAR T-cells, BiTEs, and ICBs, and suggests ways to improve outcomes.

Keywords:
CAR-T cell therapyacute lymphoblastic leukemiaacute myeloid leukemiabi-specific T cell engagersimmune checkpoint blockadeimmune-based therapy

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Area of Science:

  • Hematology
  • Immunology
  • Oncology

Background:

  • Treatment resistance is a major cause of mortality in acute leukemia.
  • Novel immune-based therapies, including chimeric antigen receptor (CAR) T-cells, bi-specific T-cell engagers (BiTEs), and immune checkpoint blockers (ICBs), show promise for chemoresistant B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML).
  • However, resistance to these advanced immunotherapies remains a significant clinical challenge.

Purpose of the Study:

  • To review critical insights gained from immune-based therapies targeting high-risk B-ALL and AML.
  • To identify leukemia-intrinsic and -extrinsic mechanisms underlying treatment resistance.
  • To discuss strategies for enhancing the efficacy of current immune-based treatment regimens.

Main Methods:

  • This review synthesizes current literature on immune-based therapies for B-ALL and AML.
  • It analyzes mechanisms of treatment resistance, categorizing them into leukemia-intrinsic and -extrinsic factors.
  • The review discusses potential alternative approaches to overcome resistance.

Main Results:

  • Leukemia-intrinsic resistance mechanisms include target antigen loss and tumor heterogeneity.
  • Extrinsic resistance factors involve the immunosuppressive tumor microenvironment.
  • These mechanisms contribute to the limited effectiveness of CAR T-cells, BiTEs, and ICBs in a subset of patients.

Conclusions:

  • Understanding resistance mechanisms is crucial for improving outcomes in B-ALL and AML.
  • Combining insights into intrinsic and extrinsic resistance can guide the development of more effective immune-based strategies.
  • Further research into overcoming these resistance pathways is essential for advancing leukemia treatment.