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Related Experiment Videos

Anett Pfeiffer1, Frederic B Thalheimer1, Sylvia Hartmann2

  • 1Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.

EMBO Molecular Medicine
|September 19, 2018
PubMed
Summary

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This summary is machine-generated.

Researchers developed a novel method for in vivo generation of chimeric antigen receptor (CAR) T cells targeting CD19+ B cells. This approach shows promise for treating B-cell malignancies but carries risks of cytokine release syndrome.

Area of Science:

  • Immunology
  • Gene Therapy
  • Oncology

Background:

  • Chimeric antigen receptor (CAR) T cells offer significant therapeutic benefits for B-cell malignancies.
  • Current CAR T-cell manufacturing is complex, limiting widespread availability.
  • Developing simplified CAR T-cell production methods is crucial for broader clinical application.

Purpose of the Study:

  • To investigate the feasibility of generating CD19-CAR T cells directly in vivo.
  • To assess the efficacy and safety of lentiviral vector-mediated in vivo CAR T-cell generation.

Main Methods:

  • Utilized a lentiviral vector (CD8-LV) targeting human CD8+ cells for in vivo gene delivery.
  • Administered CD8-LV to mice xenografted with Raji lymphoma cells and human peripheral blood mononuclear cells.
Keywords:
T‐cell targetingcytokine release syndromegene deliveryhumanized mouse

Related Experiment Videos

  • Evaluated CAR expression, B-cell depletion, and adverse effects in treated animals.

    • Main Results:

    • Successfully generated CD19-CAR T cells specifically within CD8+ T cells in vivo.
    • Demonstrated efficacious elimination of CD19+ B cells in xenograft models.
    • Observed induction of CAR T cells and B-cell depletion in a majority of treated animals, with some exhibiting signs of cytokine release syndrome.

    Conclusions:

    • In vivo reprogramming of human CD8+ CAR T cells targeting CD19+ cells is feasible.
    • The in vivo approach mirrors adverse effects seen in clinical CAR T-cell therapy, such as cytokine release syndrome.
    • Further research is needed to optimize safety and efficacy for clinical translation.