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Chimeric Antigen Receptors for T-Cell Malignancies

Lauren D Scherer1,2, Malcolm K Brenner1,2,3, Maksim Mamonkin1,2,3,4

  • 1Texas Children's Hospital, Houston, TX, United States.

Frontiers in Oncology
|March 21, 2019
PubMed

Insights

Chimeric antigen receptor (CAR) T-cell therapy for T-cell cancers faces challenges. Strategies are needed to prevent CAR T-cells from attacking healthy T-cells, improving treatment safety and effectiveness.

Area of Science:

  • Immunology
  • Oncology
  • Cell Therapy

Background:

  • Chimeric antigen receptor (CAR)-modified T cells show promise for treating T-lineage leukemia and lymphoma.
  • A key challenge involves targeting tumor antigens that are also present on healthy T cells.

Purpose of the Study:

  • To review the preclinical development of CAR T-cell therapies for T-cell malignancies.
  • To discuss strategies for mitigating toxicities related to on-target fratricide and off-tumor activity.

Main Methods:

  • Review of preclinical studies on CAR T-cell therapy for T-cell malignancies.
  • Analysis of strategies to address CAR T-cell-related toxicities.

Main Results:

  • Targeting shared antigens can lead to CAR T-cell over-activation or fratricide, reducing efficacy.
  • Elimination of normal T-cell subsets by CAR T cells can cause temporary immunosuppression.

Conclusions:

  • Minimizing toxicities from on-target fratricide and off-tumor activity is crucial for successful CAR T-cell therapy in T-cell malignancies.
  • Further research into targeted strategies is essential for enhancing the safety and effectiveness of these advanced therapies.
Keywords:
T cell malignancyT-cellschimeric antigen receptors (CARs)immunotherapynon-Hodgkin lymphoma

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