Anti-EGFR×CD70 BsADC BCG020

BCG020 is a human common light chain IgG1 bispecific antibody targeting EGFR and CD70. As a first-in-class bispecific antibody, BCG020 shows significant potential for the treatment of solid tumors with high EGFR and CD70 expression.

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  • Highlights of anti-EGFR×CD70 bsADC
  • About EGFR and CD70

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    Highlights of anti-EGFR×CD70 bsADC
    • The bsAb A01B01 (BCG020) is a human, common light chain, IgG1 bispecific antibody targeting EGFR and CD70.
    • The parental antibody A01 shows high affinity to both human and monkey EGFR, high internalization activity in EGFR+ tumor cell lines, and can prevent ligand binding. The parental antibody B01 shows high affinity to both human and monkey CD70, high internalization activity in CD70+ tumor cell lines, and can suppress CD70-induced signaling of CD27-Luc.
    • In vitro, the bsAb BCG020 shows high affinity to both hEGFR and hCD70, and high internalization activity in EGFR+ and CD70+ tumor cells.
    • In the established CDX models, EGFR×CD70 bsAb potently inhibited DU-145 and SK-OV-3 tumor growth at 10 mg/kg.
    • These data indicate that BCG020 is a first-in-class, targeted to treat solid tumors with EGFR and CD70 high expression.
    BCG020 bsAb shows high affinity to both hEGFR and hCD70

    RenLite-derived A01 mAb and B01 mAb are assembled into a common light chain bispecific antibody BCG020.

    Capture Analyte ka (1/Ms) kd (1/s) KD (M)
    Positive control-1 Human EGFR 1.61E+05 1.14E-03 7.07E-09
    Positive control-2 Human CD70 4.314E+05 1.592E-04 3.689E-10
    BCG020 Human EGFR 2.46E+05 9.73E-04 3.96E-09
    Human CD70 8.947E+05 2.028E-04 2.266E-10

    *Positive control-1 is Amivantamab analog
    Positive control-2 is ARGX-110 analog

    The single-concentration kinetics of antibody was tested by Surface Plasmon Resonance (SPR) or Bio-Layer Interferometry(BLI).

    BCG020 bsAb exhibits high internalization activity in DU145 cells (EGFR+/CD70+)

    *Positive control-1 is Amivantamab
    *Positive control-2 is ARGX-110

    High internalization activity of BCG020 in DU145(EGFR+/CD70+). After 2.5 μg/mL Isotype control, positive controls or BCG020 treatment for 5 hours, the fluorescence signal was detected in DU145 cells by flow cytometry.

    BCG020 bsAb inhibits tumor growth in the DU-145 and SK-OV-3 xenograft model

    DU-145(EGFR+/CD70+) and SK-OV-3 (EGFR+/CD70+) cell line-derived xenograft (CDX) models were used to test efficacy of BCG020. Antibodies were dosed at 10 mg/kg two times per week i.p. (5 animals/group).

    About EGFR and CD70

    The epidermal growth factor receptor (EGFR) is highly expressed across a wide range of different cancers and is a known driver of cancer growth; EGFR upregulation is frequently associated with adverse prognosis. Many patients undergoing EGFR-TKI (tyrosine kinase inhibitors) treatment will acquire resistance, which can be accompanied by increased expression of CD70 in some cancers. Simultaneous engagement of both EGFR and CD70 with a bispecific antibody (bsAb) is a potential strategy to overcome such resistance and achieve greater efficacy.

    Learn more about the RenLite and ADC platform.