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Related Experiment Video

Updated: Mar 7, 2026

A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
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A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells

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Fully human CD19-specific chimeric antigen receptors for T-cell therapy.

D Sommermeyer1, T Hill1, S M Shamah2

  • 1Fred Hutchinson Cancer Research Center, Clinical Research Division, Program in Immunology, Seattle, WA, USA.

Leukemia
|February 17, 2017
PubMed
Summary

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Researchers developed fully human CD19-specific chimeric antigen receptor (CAR) T-cells to treat B-cell malignancies. These human CAR T-cells show reduced immunogenicity and effectively eliminate tumors, potentially improving patient outcomes in cancer immunotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Adoptive transfer of CD19-specific chimeric antigen receptor (CAR) T-cells has shown success in treating B-cell malignancies.
  • Immune responses against murine single-chain variable fragments (scFv) in CARs can lead to CAR T-cell elimination and tumor relapse.

Purpose of the Study:

  • To generate fully human CD19-specific scFvs with binding characteristics similar to the murine FMC63 scFv.
  • To construct and evaluate novel CAR T-cells using these human scFvs to reduce immunogenicity and improve efficacy.
  • To assess the safety and efficacy of human CAR T-cells in preclinical models.

Main Methods:

  • Generated fully human scFvs using human antibody DNA libraries.
  • Constructed various CAR formats with human scFvs and transduced primary human T-cells.

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  • Assessed CAR T-cell activation against CD19-positive cell lines and primary chronic lymphocytic leukemia cells.
  • Evaluated tumor elimination in human lymphoma xenografts in immunodeficient mice.
  • Performed imaging to analyze CAR T-cell surface distribution and signaling.

    • Main Results:

    • Fully human CD19-specific CAR T-cells were generated and demonstrated specific activation against CD19-positive targets.
    • These human CAR T-cells effectively eliminated human lymphoma xenografts in vivo.
    • Certain fully human CAR constructs outperformed the widely used murine FMC63-based CAR.
    • No evidence of CAR T-cell clustering or tonic signaling was observed with human CARs.
    • Modified fusion sites further reduced potential immunogenicity.

    Conclusions:

    • Fully human CD19-specific CARs offer a promising alternative to murine-based CARs, potentially reducing immune rejection.
    • These novel CAR constructs may enhance the safety and durability of CAR T-cell therapy for B-cell malignancies.
    • The developed human CARs are suitable for targeting validated clinical targets, with potential for reduced adverse immune responses.