Anti-5T4 x MUC1 BsADC BCG016

A novel bispecific ADC targeting 5T4 and the cleaved MUC1-C protein, which remains membrane-bound on tumor cells. The 5T4-MUC1 bsADC showed superior anti-tumor efficacy in a PDX model and has the potential to be a novel therapeutic for 5T4 and MUC1 co-expressing tumors.

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  • Highlights of anti-5T4 x MUC1 bsADC
  • 5T4×MUC1 bsAb shows enhanced binding and internalization
  • The anti-5T4 and anti-MUC1 conjugates show potent in vivo efficacy in PDX models
  • About 5T4 and MUC1

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    Highlights of anti-5T4 x MUC1 bsADC
    • 5T4 is an oncofetal tumor-associated antigen (TAA) that is co-expressed with MUC1 in various tumors.
    • We identified an anti-5T4 antibody with high affinity and specificity and an anti-MUC1 antibody targeting the juxtamembrane epitope of MUC1, both of which antibody conjugates showed strong efficacy in vivo compared to benchmark ADCs.
    • The 5T4×MUC1 bsAb binds a variety of tumor lines, including pancreatic, breast, prostate, and lung cancers.
    • The 5T4×MUC1 bsAb demonstrates higher endocytosis and tumor growth inhibition for 5T4/MUC1 co-expressing tumor cells.
    • BCG016-vcMMAE showed improved efficacy in a lung PDX model, outperforming benchmark ADCs.
    5T4×MUC1 bsAb shows enhanced binding and internalization

    (A-D) The 5T4×MUC1 bsAb with binding and internalization in two cell lines. The 5T4×MUC1 bsAb showed stronger binding than benchmarks in two cell lines and with higher binding activity than its parental antibodies in HCC1954 (A,B). Accordingly, the endocytosis activity in two cell lines reflects consistent results with binding (C,D).

    The anti-5T4 and anti-MUC1 conjugates show potent in vivo efficacy in PDX models

    The anti-5T4 vcMMAE and anti-MUC1 vcMMAE exhibit superior, or at least comparable, efficacy relative to the 5T4 and MUC1 benchmark ADCs, respectively. Both show more potent activity than their benchmark ADC in PDX models with low 5T4 and moderate MUC1 expression, respectively. All ADCs carried the same payload (vcMMAE) with the same DAR of ~4. The 5T4 and MUC1 expression in the PDX model are shown and the H-score is labeled.

    About 5T4 and MUC1

    5T4 is an oncofetal antigen that is frequently overexpressed in solid tumors with adverse clinical outcomes and is an attractive therapeutic target due to its low expression in normal adult tissues. While several therapeutic agents targeting 5T4 antigen are currently being evaluated in human clinical trials, none have yet entered the market. Another target, MUC1, is currently under clinical investigation, with most drugs in clinical trials showing limited efficacy due to the shedding of the target antigen MUC1-N. 5T4 and MUC1 are commonly co-expressed in various solid tumors, including lung, breast, colorectal, and pancreatic cancers, suggesting that targeting both antigens with a bispecific ADC (bsADC) could be a promising therapeutic strategy.

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