RenMice-Drug Discovery Engine

RenTCR™

RenTCR™ mice carry human TCRα/β gene loci and human HLA molecules, enabling in vivo T-cell selection and immune education for the discovery of fully human TCRs with high diversity, specificity, and binding activity to support TCR-based therapeutics.
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  • Key Features
  • Validation Data

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    Key Features

    RenTCR™ mice carry human TCRα/β gene loci and human HLA molecules, enabling fully human TCRs to undergo natural selection and immune education in vivo and generate functional TCR repertoires with high specificity, binding activity, and stability. Following immunization, RenTCR™ mice generate robust antigen-specific T-cell responses, enabling efficient discovery of fully human TCR sequences from activated T cells. These TCRs can be further evaluated for in vitro function, affinity, specificity, and in vivo antitumor activity, supporting the development of TCR-T cell therapies and soluble TCR therapeutics.
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    RenTCR™ Mice Enable Discovery of High-Affinity Fully Human TCRs

    RenTCR™ Mice Enable Discovery of High-Affinity Fully Human TCRs img

    RenTCR™ Mouse Models

    Mouse Model F0 Chimeric Mouse Heterozygous Mouse Homozygous Mouse Phenotypic Analysis
    MHC-I HLA-A0201
    HLA-A1101
    HLA-A2402
    HLA-A0101
    HLA-A0301
    HLA-B0702
    HLA-B1501
    HLA-A3303
    HLA-B2705
    MHC-II HLA-DRB1*0301
    HLA-DRB1*0401
    HLA-DRB1*0701

    TCR Repertoire in RenTCR™ Mice

    TCR Repertoire in RenTCR™ Mice img
    Fig. 1. TCR repertoires in RenTCR™ mice. RNA-seq was used to analyze TCRα and TCRβ repertoire profiles in RenTCR™ mice. (a, b) Frequencies of V and J gene usage in the TCRα and TCRβ repertoires in naïve splenic T cells from RenTCR™ mice (n = 2). Almost all functional genes were detected. Data are shown as mean ± SEM. (c) CDR3 length (bp) in RenTCR™ mice (n = 1). CDR3 lengths and their distribution are consistent with those observed in humans.

    Validation Data

    RenTCR™ platform-derived HLA-A2.1/MAGEA1-specific TCRs exhibited higher peptide sensitivity than human donor–derived TCRs
    Validation Data img 1
    Validation Data img 2
    IFN-γ production by TCR-transduced human T cells in response to stimulation with MAGEA1 peptide-loaded T2 cells. Human donor-derived TCRs include those in clinical development or reported in the literature. Data are normalized to maximum IFN-γ release and fitted to a four-parameter logistic model.
    Validation Data img 3
    Tumor (A375, human HLA-A*02:01+) growth inhibition
    Validation Data img 4
    Tumor (SHP-77, human HLA-A*02:01+ ) growth inhibition
    Validation Data img 5
    NDG immunodeficient mice were implanted with human HLA-A*02:01+ tumor cell lines A375 and SHP-77, both of which endogenously express MAGE-A4. Once the tumor volume reached 100 mm3, T cells expressing MAGE-A4-specific TCRs or mock T cells were administered (n = 6 mice/group), with T cells transduced with clinical-stage affinity-enhanced TCRs serving as positive controls. S.C.: subcutaneous injection; I.V.: intravenous injection; TIW: three times a week.