CD138 as a target antigen of personalized cancer therapy

CD138 as a target antigen of personalized cancer therapy

CD138 (syndecan-1) is highly expressed on the surface of multiple myeloma cells and is the target antigen of the antibody-drug conjugate (ADC) BT-062 (indatuximab ravtansine), which is in clinical development for anti-tumor therapy in patients with this disease. BT-062 comprises an anti-CD138 chimeric antibody linked to a toxin (DM4) via a chemical linker using the antibody-drug conjugate technology developed by ImmunoGen, Inc.

CD138 is also found on some types of solid tumors, including certain breast and bladder cancers. The available preclinical data in mice implanted with human CD138-positive solid tumors show a very high activity of BT-062 against these tumors, even at low doses.

The aim of the project is to gain clinical data for the individualized treatment of patients with CD138-expressing solid tumors.

The following steps are planned:

  1. Evaluating CD138 as a target antigen for treating tumors: a) IHC analysis of tumor blocks (distribution of intensity within a tumor sample), b) determining the percentage of CD138 positive tumors within one indication (analysis of tumor arrays), c) optimizing the IHC assay
  2. Develop an animal model to test specific toxicity for the ADC BT-062
  3. Conducting a Phase I/IIa trial with patients with CD138-positive solid tumors
    - Selecting patients based on the expression of CD138 on biopsy material
    - Determine tolerability and gather initial evidence of anti-tumor activity in patients with CD138-positive solid tumors

This personalized approach to therapy aims to ensure that patients with adequate CD138 expression in particular – and thus with a high probability of response – are included in the clinical trial.

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Keywords 

  • BT062
  • solid tumors
  • antibody drug conjugate
  • ADC
  • CD138
  • Syndecan
  • targeted therapy
  • personalized medicine

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